Cyclic malonamides as inhibitors of abeta protein production

ABSTRACT

This invention relates to novel cyclic malonamides having the formula (I): 
     
       
         
         
             
             
         
       
     
     to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer&#39;s disease and Down&#39;s Syndrome.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/433,925 filed May 1, 2009, which is a continuation of U.S. patentapplication Ser. No. 12/142,145, filed Jun. 19, 2008 (U.S. Pat. No.7,528,249), which is a continuation of U.S. patent application Ser. No.11/841,081, filed Aug. 20, 2007 (U.S. Pat. No. 7,390,896), which is acontinuation of U.S. patent application Ser. No. 11/327,721, filed Jan.6, 2006 (U.S. Pat. No. 7,276,496), which is a continuation of U.S.patent application Ser. No. 10/746,769, filed Dec. 24, 2003 (U.S. Pat.No. 7,053,081), which is a continuation of U.S. patent application Ser.No. 09/825,211, filed Apr. 3, 2001 (U.S. Pat. No. 6,759,404), whichclaims priority from U.S. Provisional Application Ser. No. 60/194,503,filed Apr. 3, 2000 (expired), the contents of which are herebyincorporated by reference herein in their entirety.

FIELD OF THE INVENTION

This invention relates to novel cyclic malonamides having drug andbio-affecting properties, their pharmaceutical compositions and methodsof use. These novel compounds inhibit the processing of amyloidprecursor protein and, more specifically, inhibit the production ofAβ-peptide, thereby acting to prevent the formation of neurologicaldeposits of amyloid protein. More particularly, the present inventionrelates to the treatment of neurological disorders related to β-amyloidproduction such as Alzheimer's disease and Down's Syndrome.

BACKGROUND OF THE INVENTION

Alzheimer's disease (AD) is a degenerative brain disorder characterizedclinically by progressive loss of memory, temporal and localorientation, cognition, reasoning, judgment and emotionally stability.AD is a common cause of progressive dementia in humans and is one of themajor causes of death in the United States. AD has been observed in allraces and ethnic groups worldwide, and is a major present and futurehealth problem. No treatment that effectively prevents AD or reversesthe clinical symptoms and underlying pathophysiology is currentlyavailable (for review, Dennis J. Selkoe; Cell Biology of the amyloid(beta)-protein precursor and the mechanism of Alzheimer's disease, AnnuRev Cell Biol, 1994, 10: 373-403).

Histopathological examination of brain tissue derived upon autopsy orfrom neurosurgical specimens in effected individuals revealed theoccurrence of amyloid plaques and neurofibrillar tangles in the cerebralcortex of such patients. Similar alterations were observed in patientswith Trisomy 21 (Down's syndrome), and hereditary cerebral hemorrhagewith amyloidosis of the Dutch-type. Neurofibrillar tangles arenonmembrane-bound bundles of abnormal proteinaceous filaments andbiochemical and immunochemical studies led to the conclusion that theirprinciple protein subunit is an altered phosphorylated form of the tauprotein (reviewed in Selkoe, 1994).

Biochemical and immunological studies revealed that the dominantproteinaceous component of the amyloid plaque is an approximately 4.2kilodalton (kD) protein of about 39 to 43 amino acids. This protein wasdesignated Aβ, β-amyloid peptide, and sometimes β/A4; referred to hereinas Aβ. In addition to its deposition in amyloid plaques, Aβ is alsofound in the walls of meningeal and parenchymal arterioles, smallarteries, capillaries, and sometimes, venules. Aβ was first purified anda partial amino acid reported in 1984 (Glenner and Wong, Biochem.Biophys. Res. Commun. 120: 885-890). The isolation and sequence data forthe first 28 amino acids are described in U.S. Pat. No. 4,666,829.

Compelling evidence accumulated during the last decade revealed that Aβis an internal polypeptide derived from a type 1 integral membraneprotein, termed β amyloid precursor protein (APP). β APP is normallyproduced by many cells both in vivo and in cultured cells, derived fromvarious animals and humans. Aβ is derived from cleavage of β APP by asyet unknown enzyme (protease) system(s), collectively termed secretases.

The existence of at least four proteolytic activities has beenpostulated. They include β secretase(s), generating the N-terminus ofAβ, α secretase(s) cleaving around the 16/17 peptide bond in Aβ, and γsecretases, generating C-terminal Aβ fragments ending at position 38,39, 40, 42, and 43 or generating C-terminal extended precursors whichare subsequently truncated to the above polypeptides.

Several lines of evidence suggest that abnormal accumulation of Aβ playsa key role in the pathogenesis of AD. Firstly, Aβ is the major proteinfound in amyloid plaques. Secondly, Aβ is neurotoxic and may be causallyrelated to neuronal death observed in AD patients. Thirdly, missense DNAmutations at position 717 in the 770 isoform of β APP can be found ineffected members but not unaffected members of several families with agenetically determined (familiar) form of AD. In addition, several otherβ APP mutations have been described in familiar forms of AD. Fourthly,similar neuropathological changes have been observed in transgenicanimals overexpressing mutant forms of human β APP. Fifthly, individualswith Down's syndrome have an increased gene dosage of β APP and developearly-onset AD. Taken together, these observations strongly suggest thatAβ depositions may be causally related to the AD.

It is hypothesized that inhibiting the production of Aβ will prevent andreduce neurological degeneration, by controlling the formation ofamyloid plaques, reducing neurotoxicity and, generally, mediating thepathology associated with Aβ production. One method of treatment methodswould therefore be based on drugs that inhibit the formation of Aβ invivo.

Methods of treatment could target the formation of Aβ through theenzymes involved in the proteolytic processing of β amyloid precursorprotein. Compounds that inhibit β or γ secretase activity, eitherdirectly or indirectly, could control the production of Aβ.Advantageously, compounds that specifically target γ secretases, couldcontrol the production of Aβ. Such inhibition of β or γ secretases couldthereby reduce production of Aβ, which, thereby, could reduce or preventthe neurological disorders associated with Aβ protein.

PCT publication number WO 96/29313 discloses the general formula:

covering metalloprotease inhibiting compounds useful for the treatmentof diseases associated with excess and/or unwanted matrixmetalloprotease activity, particularly collagenase and or stromelysinactivity.

Compounds of general formula:

are disclosed in PCT publication number WO 95/22966 relating to matrixmetalloprotease inhibitors. The compounds of the invention are usefulfor the treatment of conditions associated with the destruction ofcartilage, including corneal ulceration, osteoporosis, periodontitis andcancer.

European Patent Application number EP 0652009A1 relates to the generalformula:

and discloses compounds that are protease inhibitors that inhibit Aβproduction.

U.S. Pat. No. 5,703,129 discloses the general formula:

which covers 5-amino-6-cyclohexyl-4-hydroxy-hexanamide derivatives thatinhibit Aβ production and are useful in the treatment of Alzheimer'sdisease.

Copending, commonly assigned U.S. patent application Ser. No. 09/370,089filed Aug. 7, 1999 (equivalent to international application PCTUS99/17717) discloses lactams of general formula:

wherein the lactam ring B is substituted by succinamide and acarbocyclic, aryl, or heteroaryl group. These compounds inhibit theprocessing of amyloid precursor protein and, more specifically, inhibitthe production of Aβ-peptide, thereby acting to prevent the formation ofneurological deposits of amyloid protein.

None of the above references teaches or suggests the compounds of thepresent invention which are described in detail below.

SUMMARY OF THE INVENTION

One object of the present invention is to provide novel compounds whichare useful as inhibitors of the production of Aβ protein orpharmaceutically acceptable salts or prodrugs thereof.

It is another object of the present invention to provide pharmaceuticalcompositions comprising a pharmaceutically acceptable carrier and atherapeutically effective amount of at least one of the compounds of thepresent invention or a pharmaceutically acceptable salt or prodrug formthereof.

It is another object of the present invention to provide a method fortreating degenerative neurological disorders comprising administering toa host in need of such treatment a therapeutically effective amount ofat least one of the compounds of the present invention or apharmaceutically acceptable salt or prodrug form thereof.

These and other objects, which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat compounds of Formula (I):

or a stereoisomer, pharmaceutically acceptable salt or prodrug formsthereof, wherein R³, R⁶, B, C, W, X, Y, and Z are defined below, areeffective inhibitors of the production of Aβ.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Thus, in a first embodiment, the present invention provides a novelcompound of Formula (I):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein:

-   -   L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or        —NR²⁶C(═O)NR²⁶—;

-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(l)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—O—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—N(R^(7b))C(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—C(═O)N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—N(R^(7b))S(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(l)—S(═O)₂N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;

-   n is 0, 1, 2, or 3;

-   m is 0, 1, 2, or 3;

-   l is 1, 2, or 3;

-   Ring C is a 3 to 8 membered carbocycle,    -   wherein the carbocycle is saturated or partially saturated;    -   optionally, the carbocycle contains a heteroatom selected from        —O—, —S—, —S(═O)—, —S(═O)₂—, and —N(R²⁰)—; and    -   wherein the carbocycle is substituted with 0-4 R²¹;

-   R⁴ is H, OH, OR^(14a),    -   C₁-C₈ alkyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R⁶ is H;    -   C₁-C₆ alkyl substituted with 0-3 R^(6a);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(6b); or    -   C₆-C₁₀ aryl substituted with 0-3 R^(6b);

-   R^(6a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃;

-   R^(6b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;

-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, C₁-C₄ alkyl, phenyl substituted with 0-5    R^(7c);

-   R^(7a), at each occurrence, is independently selected from H, Cl, F,    Br, I, CN, CF₃, and C₁-C₄ alkyl;

-   R^(7b) is independently selected from H and C₁-C₄ alkyl;

-   R^(7c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, CF₃, C₁-C₄ alkoxy, and C₁-C₄ alkyl;

-   B is a 5 to 10 membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains an additional heteroatom        selected from —O—, —S—, —S(═O)—, —S(═O)₂—, —N═, —NH—, and        —N(R¹⁰)—;

-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(10b);

-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, aryl    substituted with 0-4 R^(10b); C₃-C₁₀ carbocycle substituted with 0-3    R^(10b), and 5 to 10 membered heterocycle containing 1 to 4    heteroatoms selected from nitrogen, oxygen, and sulphur, wherein    said 5 to 10 membered heterocycle is substituted with 0-3 R^(10b);

-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,    acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄    haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹¹, at each occurrence, is independently selected from H, C₁-C₄    alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,    C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(11b);

-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   additionally, two R¹¹ substituents on adjacent atoms may be combined    to form a 5 to 6 membered heteroaryl fused radical, wherein said 5    to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms    selected from N, O, and S; wherein said 5 to 6 membered heteroaryl    fused radical is substituted with 0-3 R¹³;

-   additionally, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle substituted with    0-3 R¹³;

-   additionally, two R¹¹ substituents on adjacent atoms may be combined    to form a benzo fused radical; wherein said benzo fused radical is    substituted with 0-4 R¹³;

-   W is (CR⁸R^(8a))_(p)—;

-   p is 0, 1, 2, 3, or 4;

-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl and C₃-C₈    cycloalkyl;

-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);

-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ halothioalkoxy;

-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;

-   t is 0, 1, 2, or 3;

-   u is 0, 1, 2, or 3;

-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₆ alkyl and C₃-C₈ cycloalkyl;

-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,    —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 1-3 R¹²;    -   C₂-C₄ alkenyl substituted with 1-3 R¹²;    -   C₂-C₄ alkynyl substituted with 1-3 R¹²;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₄ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₄ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R¹², at each occurrence, is independently selected from C₆-C₁₀ aryl    substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R¹⁴ is H, phenyl substituted with 0-4 R^(14b), benzyl substituted    with 0-4 R^(14b), C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆    cycloalkyl;

-   R^(14a) is H, C₆-C₁₀ aryl, benzyl, heterocycle, or C₁-C₄ alkyl;

-   R^(14b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, aryl-(C₁-C₆ alkyl)- wherein the aryl is substituted with 0-4    R^(15b), (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—;

-   R^(15b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆    alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄    haloalkyl-S—;

-   R¹⁶, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;

-   R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, aryl substituted by 0-4    R^(17a), or —CH₂-aryl substituted by 0-4 R^(17a);

-   R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃,    SO₂CH₃, —NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;

-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;

-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;

-   R²⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl optionally substituted with 0-2 R^(20a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(20b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(20b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(20b);

-   R^(20a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, F, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, aryl substituted with 0-4    R^(20b), and heterocycle substituted with 0-4 R^(20b);

-   R^(20b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,    acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄    haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R²¹, at each occurrence, is independently selected from H, C₁-C₄    alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,    C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(21a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(21b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(21b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(21b);

-   R^(21a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;    -   phenyl substituted with 0-3 R^(21b);    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(21b); and    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(21b);

-   R^(21b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   additionally, two R²¹ substituents on adjacent atoms may be combined    to form a 5 to 6 membered heteroaryl fused radical, wherein said 5    to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms    selected from N, O, and S; wherein said 5 to 6 membered heteroaryl    fused radical is substituted with 0-3 R²³;

-   additionally, two R²¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle substituted with    0-3 R²³;

-   additionally, two R²¹ substituents on adjacent atoms may be combined    to form a benzo fused radical; wherein said benzo fused radical is    substituted with 0-4 R²³;

-   R²³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R²⁶ is H;    -   C₁-C₆ alkyl substituted with 0-3 R^(26a);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(26b); or    -   C₆-C₁₀ aryl substituted with 0-3 R^(26b);

-   R^(26a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃; and

-   R^(26b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy.

[2] In a preferred embodiment the present invention provides a compoundof Formula (I), wherein:

-   -   L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, or —OC(═O)NR²⁶—;

-   R³ is —(CHR⁷)_(n)—R⁴,    -   —(CHR⁷)_(l)—N—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CHR⁷)_(l)—O—(CR⁷R^(7a))_(m)—R⁴;

-   n is 0, 1 or 2;

-   m is 0, 1 or 2;

-   l is 1;

-   Ring C is a 3 to 8 membered carbocycle substituted with 0-4 R²¹;    optionally, the carbocycle contains a heteroatom selected from —O—    and —N(R²⁰)—;

-   R⁴ is H, OH, OR^(14a),    -   C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-1 R^(4a),    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), and    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy;

-   R⁶ is H;

-   R⁷, at each occurrence, is independently selected from H, OH, F,    CF₃, methyl, and ethyl;

-   Ring B is a 7 membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from —O—,        —S—, —S(═O)—, —S(═O)₂—, —N═, —NH—, and —N(R¹⁰)—;

-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl optionally substituted with 0-2 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(10b);

-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, phenyl    substituted with 0-4 R^(10b); and 5 to 10 membered heterocycle    containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and    sulphur, wherein said 5 to 10 membered heterocycle is substituted    with 0-3 R^(10b);

-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R¹¹, at each occurrence, is independently selected from H, C₁-C₄    alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,    C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(11b);

-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;

-   additionally, two R¹¹ substituents on adjacent atoms may be combined    to form a benzo fused radical; wherein said benzo fused radical is    substituted with 0-2 R¹³;

-   additionally, two R¹¹ substituents on adjacent atoms may be combined    to form a 5 to 6 membered heteroaryl fused radical, wherein said 5    to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms    selected from N, O, and S; wherein said 5 to 6 membered heteroaryl    fused radical is substituted with 0-2 R¹³;

-   additionally, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle substituted with    0-2 R¹³;

-   W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—;

-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;

-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,

-   Z is H; C₁-C₆ alkyl; C₂-C₄ alkenyl; C₂-C₄ alkynyl,    -   C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₂-C₃ alkenyl substituted with 1-2 R¹²;    -   C₂-C₃ alkynyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);

-   R¹², at each occurrence, is independently selected from    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;

-   R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₄    alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄    alkyl)-S(═O)₂—;

-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄    alkyl)-S(═O)₂—;

-   R¹⁷ is H, methyl, ethyl, propyl, butyl, methoxymethyl, ethoxymethyl,    methoxyethyl, ethoxyethyl,    -   phenyl substituted by 0-3 R^(17a), or    -   —CH₂-phenyl substituted by 0-3 R^(17a);

-   R^(17a) is H, methyl, methoxy, —OH, F, Cl, CF₃, or OCF₃;

-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

-   R¹⁹, at each occurrence, is independently selected from H, methyl,    and ethyl;

-   R²⁰ is H or C(═O)OR¹⁷;

-   R²⁶ is H, methyl, or ethyl.

[3] In another preferred embodiment the present invention provides acompound of Formula (I), wherein:

-   Ring C is selected from:

-   wherein Ring C is substituted with 0-2 R²¹; and-   Ring B is selected from:

[4] In another more preferred embodiment the present invention providesa compound of Formula (I), wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

-   R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-1 R^(4a), or    -   C₂-C₆ alkynyl substituted with 0-1 R^(4a);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenyl substituted        with 0-3 R^(4b), and    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b); wherein        said 5 to 6 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, and tetrazolyl;

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;

-   W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—;

-   X is a bond, phenyl, C₃-C₆ cycloalkyl, or    -   5 to 6 membered heterocycle;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,

-   Z is H; C₁-C₆ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl,    -   C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₂-C₃ alkenyl substituted with 1-2 R¹²;    -   C₂-C₃ alkynyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(12b); wherein        said 5 to 6 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, and tetrazolyl;

-   R¹², at each occurrence, is independently selected from    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b); wherein        said 5 to 6 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, and tetrazolyl;

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;

-   R¹³, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN,    NR¹⁵R¹⁶, and CF₃;

-   R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl;

-   R¹⁶, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,    ethyl-C(═O)—, methyl-S(═O)₂—, ethyl-S(═O)₂—, and propyl-S(═O)₂—;

-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

-   R¹⁹, at each occurrence, is independently selected from H, methyl,    and ethyl;

-   R²⁰ is H.

[5] In another more preferred embodiment the present invention providesa compound of Formula (I), wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,    —CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃,    —CH₂CF₃, —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂,    —CH(OH)CH(CH₃)₂, —CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃,    —CF₂CH₂CH(CH₃)₂, —CH(NHCH₃)CH₂CH(CH₃)₂,    —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-, cyclopentyl-,    cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,    cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,    cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,    1—NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,    (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,    (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,    (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,    (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,    (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,    (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,    (3-Cl—F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,    phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;

-   Ring C is selected from:

-   Ring B is selected from:

-   wherein each benzo fused ring is substituted with 0-1 R¹³;-   W is a bond or —CH₂—;-   X is a bond;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Z is phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,    3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,    2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,    2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,    3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,    3-Cl—F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl,    2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl,    4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl,    thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl,    1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl, cyclopropyl,    cyclobutyl, cyclopentyl, cyclohexyl, morpholino, N-piperinyl,    phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—,    (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂, (4-Cl-phenyl)CH₂—,    (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—,    (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—,    (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—,    (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—,    (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—, (3-Cl—F-phenyl)CH₂—,    (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—,    (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—,    (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—,    (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—,    (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—, (2-Me-pyridyl)CH₂—,    (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—, (1-imidazolyl)CH₂—,    (oxazolyl)CH₂—, (isoxazolyl)CH₂—, (1-benzimidazolyl)CH₂—,    (cyclopropyl)CH₂—, (cyclobutyl)CH₂—, (cyclopentyl)CH₂—,    (cyclohexyl)CH₂—, (morpholino)CH₂—, (N-piperidinyl)CH₂—,    phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, (3-Cl—F-phenyl)CH₂CH₂—,    (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—, (4-MeO-phenyl)CH₂CH₂—,    (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—, (4-Me-phenyl)CH₂CH₂—,    (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—, (4-MeS-phenyl)CH₂CH₂—,    (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,    (4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,    (pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,    (4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,    (isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,    (cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,    (morpholino)CH₂CH₂—, or (N-piperidinyl)CH₂CH₂—;-   R¹⁰ is H, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,    (4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl,    (4-CH₃-phenyl)CH₂—, (4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl,    (4-CF₃-phenyl)CH₂—, or (4-CF₃-phenyl)CH₂CH₂—;-   R¹¹, at each occurrence, is independently selected from H, ═O,    methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 3-F-phenyl, (3-F-phenyl)CH₂—,    (3-F-phenyl)CH₂CH₂—, 2-F-phenyl, (2-F-phenyl)CH₂—,    (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,    (4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,    (3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,    (4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,    (3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,    (4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, and    pyrid-4-yl;-   R¹³, at each occurrence, is independently selected from H, F, Cl,    OH, —CH₃, —CH₂CH₃, —OCH₃, and —CF₃; and-   R²⁰ is H.

In another preferred embodiment the present invention provides acompound of Formula (I), wherein:

-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(l)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(l)—O—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(l)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;-   n is 0, 1, or 2;-   m is 0, 1, or 2;-   l is 1 or 2;-   Ring C is a 3 to 8 membered carbocycle substituted with 0-4 R²¹;    optionally, the carbocycle contains a heteroatom selected from —O—,    and —N(R²⁰)—;-   R⁴ is H, OH, OR^(14a),    -   C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, Br, I, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁶ is H, methyl, or ethyl;-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, phenyl and C₁-C₄ alkyl;-   R^(7a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;-   R^(7b) is independently selected from H, methyl, ethyl, propyl, and    butyl;-   Ring B is a 7 membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from, —O—,        —S—, —S(═O)—, —S(═O)₂—, —N═, —NH—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl optionally substituted with 0-2 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, phenyl    substituted with 0-4 R^(10b); or 5 to 10 membered heterocycle    containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and    sulphur, wherein said 5 to 10 membered heterocycle is substituted    with 0-3 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from H, C₁-C₄    alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,    C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(11b);-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   additionally, two R¹¹ substituents on adjacent atoms may be combined    to form a benzo fused radical; wherein said benzo fused radical is    substituted with 0-3 R¹³;-   additionally, two R¹¹ substituents on adjacent atoms may be combined    to form a 5 to 6 membered heteroaryl fused radical, wherein said 5    to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms    selected from N, O, and S; wherein said 5 to 6 membered heteroaryl    fused radical is substituted with 0-3 R¹³;-   additionally, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle substituted with    0-3 R¹³;-   W is —(CR⁸R^(8a))_(p)—;-   p is 0, 1, or 2;-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₃ alkyl, C₂-C₃ alkenyl, C₂-C₃ alkynyl and C₃-C₆    cycloalkyl;-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-2 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;-   t is 0, 1, or 2;-   u is 0, 1, or 2;-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl or C₃-C₆ cycloalkyl;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, or —S(═O)NR^(19b)—;-   Z is H;    -   C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R^(14a) is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl,    -   aryl substituted by 0-4 R^(17a), or    -   —CH₂-aryl substituted by 0-4 R^(17a);-   R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃,    SO₂CH₃, —NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—; and-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—-   R²⁰ is H or C(═O)R¹⁷;-   R²¹, at each occurrence, is independently selected from H, C₁-C₄    alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,    C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(21a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(21b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(21b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(21b);-   R^(21a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;    -   phenyl substituted with 0-3 R^(21b);    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(21b); and    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(21b);-   R^(21b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;-   additionally, two R²¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle substituted with    0-3 R²³;-   additionally, two R²¹ substituents on adjacent atoms may be combined    to form a benzo fused radical; wherein said benzo fused radical is    substituted with 0-4 R²³; and-   R²³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃.

[6] In another preferred embodiment the present invention provides acompound of Formula (I):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein:

-   -   L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or        NR²⁶C(═O)NR²⁶—;

-   R³ is (CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(l)—S—R⁴,    -   —(CR⁷R^(7a))_(l)—O—R⁴;    -   —(CR⁷R^(7a))_(l)—N(R^(7b))—R⁴,    -   —(CR⁷R^(7a))_(l)—S(═O)—R⁴, or    -   —(CR⁷R^(7a))_(l)—S(═O)₂—R⁴;

-   n is 0, 1 or 2;

-   l is 1 or 2;

-   R⁴ is H,    -   C₁-C₈ alkyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-8 membered carbocycle;    -   wherein said 3-8 membered carbocycle is saturated or partially        unsaturated;    -   wherein said 3-8 membered carbocycle is substituted with 0-4        R²¹; and    -   optionally, the carbocycle contains a heteroatom selected from        —O— and —N(R²⁰)—;

-   additionally, two R²¹ substituents on adjacent atoms may be combined    to form a benzo fused radical; wherein said benzo fused radical is    substituted with 0-4 R²³;

-   additionally, two R²¹ substituents on adjacent atoms may be combined    to form a 5 to 6 membered heteroaryl fused radical, wherein said 5    to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms    selected from N, O, and S; wherein said 5 to 6 membered heteroaryl    fused radical is substituted with 0-3 R²³;

-   additionally, two R²¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle substituted with    0-3 R²³;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,    OR^(14a), C₁-C₄ alkyl, C₂-C₆ alkenyl, alkynyl, C₁-C₄ alkoxy, C₁-C₄    haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—,    -   C₃-C₆ carbocycle, phenyl, and a    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur;

-   R⁶ is H, methyl, or ethyl;

-   R⁷, at each occurrence, is independently H or C₁-C₄ alkyl;

-   R^(7a), at each occurrence, is independently H or C₁-C₄ alkyl;

-   R^(7b) is H or C₁-C₄ alkyl;

-   Ring B is selected from:

-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or aryl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ haloalkyl-S—;-   R¹¹, at each occurrence, is independently selected from H, C₁-C₄    alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,    C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(11b);-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;-   W is a bond or —(CH₂)_(p)—;-   p is 1 or 2;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ carbocycle substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃    haloalkoxy, and C₁-C₃ halothioalkoxy;-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,    —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆    cycloalkyl;-   R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl,    -   aryl substituted by 0-4 R^(17a), or    -   —CH₂-aryl substituted by 0-4 R^(17a);-   R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃,    SO₂CH₃, —NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁹, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;-   R^(19b), at each occurrence, is independently is H or C₁-C₄ alkyl;-   R²⁰ is H, C₁-C₄ alkyl, or C(═O)OR¹⁷;-   R²³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; and-   R²⁶ is H or C₁-C₄ alkyl.

[7] In another preferred embodiment the present invention provides acompound of Formula (Ia):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein:

-   -   L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or        —NR²⁶C(═O)NR²⁶—;

-   R³ is —(CHR⁷)_(n)—R⁴,    -   —(CHR⁷)_(l)—S—R⁴,    -   —(CHR⁷)_(l)—O—R⁴;    -   —(CR⁷R^(7a))_(l)—N(R^(7b))—R⁴,    -   —(CR⁷R^(7a))_(l)—S(═O)—R⁴, or    -   —(CR⁷R^(7a))_(l)—S(═O)₂—R⁴;

-   n is 0, 1 or 2;

-   l is 1 or 2;

-   R⁴ is H,    -   C₁-C₈ alkyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-8 membered carbocycle;    -   wherein said 3-8 membered carbocycle is saturated or partially        unsaturated;    -   wherein said 3-8 membered carbocycle is substituted with 0-4        R²¹;    -   optionally, the carbocycle contains a heteroatom selected from        —O—, and —N(R²⁰)—;

-   additionally, two R²¹ substituents on adjacent atoms may be combined    to form a benzo fused radical; wherein said benzo fused radical is    substituted with 0-4 R²³;

-   additionally, two R²¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle substituted with    0-3 R²³;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,    OR^(14a), C₁-C₄ alkyl, C₂-C₆ alkenyl, alkynyl, C₁-C₄ alkoxy, C₁-C₄    haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—,    -   C₃-C₆ carbocycle, phenyl, and a    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur;

-   R⁷, at each occurrence, is independently H, methyl, or ethyl;

-   R^(7b) is H, methyl, or ethyl;

-   Ring B is selected from:

-   R¹¹, at each occurrence, is independently selected from H, C₁-C₄    alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,    C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl optionally substituted with 0-3 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(11b);-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(11b); and    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;-   W is a bond or —(CH₂)_(p)—;-   p is 1 or 2;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ carbocycle substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃    haloalkoxy, and C₁-C₃ halothioalkoxy;-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    C(═O)NR^(19b), —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,    —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆    cycloalkyl;-   R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, aryl substituted by 0-4    R^(17a), or —CH₂-aryl substituted by 0-4 R^(17a);-   R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃,    SO₂CH₃, —NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;-   R¹⁹, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl;-   R²⁰ is H, C₁-C₄ alkyl, or C(═O)OR¹⁷;-   R²³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; and-   R²⁶ is H or C₁-C₄ alkyl.

[8] In another preferred embodiment the present invention provides acompound of Formula (Ic):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —(CH₂)_(n)—R⁴,    -   —(CH₂)_(l)—S—R⁴,    -   —(CH₂)_(l)—O—R⁴, or    -   —(CH₂)_(l)—N(R^(7b))—R⁴;

-   n is 0, 1 or 2;

-   l is 1 or 2;

-   R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R^(7b) is H, methyl, or ethyl;

-   Ring C is a 3-8 membered carbocycle;    -   wherein said 3-8 membered carbocycle is saturated or partially        unsaturated;    -   wherein said 3-8 membered carbocycle is substituted with 0-3        R²¹;    -   optionally, the carbocycle contains a heteroatom selected from        —O—, and —N(R²⁰)—;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,    OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   W is a bond, —CH₂—, —CH₂CH₂—;

-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or    —OC(═O)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄    alkyl)-S(═O)₂—;

-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄    alkyl)-S(═O)₂—; and

-   R²⁰ is H or C₁-C₄ alkyl.

[9] In another preferred embodiment the present invention provides acompound of Formula (Ic) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

-   R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), and    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-6 membered carbocycle;    -   wherein said 3-6 membered carbocycle is saturated or partially        unsaturated;    -   wherein said 3-6 membered carbocycle is substituted with 0-2        R²¹;    -   optionally, the carbocycle contains a heteroatom selected from        —O—, and —N(R²⁰)—;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy,    ethoxy, allyl, —OCF₃, and —SCF₃;

-   W is a bond, —CH₂—, —CH₂CH₂—;

-   X is a bond;    -   phenyl substituted with 0-1 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-1 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-1 R^(Xb);

-   R^(Xb) is selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, methoxy, ethoxy,    propoxy, and —OCF₃;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₄    alkyl, and benzyl;

-   R¹⁶, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,    ethyl-C(═O)—, methyl-S(═O)₂—, ethyl-S(═O)₂—, and propyl-S(═O)₂—; and

-   R²⁰ is H or C₁-C₄ alkyl.

[10] In another preferred embodiment the present invention provides acompound of Formula (Ic) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

-   R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a), or    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a);

-   R^(4a), at each occurrence, is independently selected from is H, OH,    F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), and    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b); wherein        said 5 to 6 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, and tetrazolyl;

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-6 membered carbocycle selected from:

-   -   wherein said 3-6 membered carbocycle is substituted with 0-1        R²¹;

-   R²¹ is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy,    ethoxy, allyl, and —OCF₃;

-   W is a bond or —CH₂—;

-   X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 membered    heterocycle;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;    -   phenyl substituted with 0-4 R^(12b);    -   C₃₋₆ carbocycle substituted with 0-4 R^(12b); and    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;

-   R¹³, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN,    NR¹⁵R¹⁶, and CF₃;

-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl; and

-   R¹⁶, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, benzyl, and phenethyl; and

-   R²⁰ is H, methyl, or ethyl.

[11] In another preferred embodiment the present invention provides acompound of Formula (Ic) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   Ring C is selected from:

-   R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,    —CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃,    —CH₂CF₃, —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂,    —CH(OH)CH(CH₃)₂, —CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃,    —CF₂CH₂CH(CH₃)₂, —CH(NHCH₃)CH₂CH(CH₃)₂,    —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-, cyclopentyl-,    cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,    cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,    cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,    1-NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,    (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,    (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,    (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,    (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,    (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,    (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,    (3-Cl—F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,    phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;-   W is a bond or —CH₂—;-   X is a bond;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,    t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl,    2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl,    2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl,    3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl,    2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl,    3-F-5-Cl-phenyl, 3-Cl—F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl,    4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl,    3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl,    4-CF₃O-phenyl, furanyl, thienyl, pyridyl, 2-Me-pyridyl,    3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl,    1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,    morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,    (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—,    (3-Cl-phenyl)CH₂, (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—,    (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—,    (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—,    (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—,    (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—,    (3-F-5-Cl-phenyl)CH₂—, (3-Cl—F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—,    (3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—,    (3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—,    (3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—,    (3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—,    (thienyl)CH₂—, (pyridyl)CH₂—, (2-Me-pyridyl)CH₂—,    (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—, (1-imidazolyl)CH₂—,    (oxazolyl)CH₂—, (isoxazolyl)CH₂—, (1-benzimidazolyl)CH₂—,    (cyclopropyl)CH₂—, (cyclobutyl)CH₂—, (cyclopentyl)CH₂—,    (cyclohexyl)CH₂—, (morpholino)CH₂—, (N-piperidinyl)CH₂—,    phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, (3-Cl—F-phenyl)CH₂CH₂—,    (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—, (4-MeO-phenyl)CH₂CH₂—,    (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—, (4-Me-phenyl)CH₂CH₂—,    (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—, (4-MeS-phenyl)CH₂CH₂—,    (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,    (4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,    (pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,    (4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,    (isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,    (cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,    (morpholino)CH₂CH₂—, or (N-piperidinyl)CH₂CH₂—;-   R¹³, at each occurrence, is independently selected from H, F, Cl,    OH, —CH₃, —CH₂CH₃, —OCH₃, or —CF₃.-   R²⁰ is H, methyl, or ethyl.

[12] In another preferred embodiment the present invention provides acompound of Formula (Id) and (Ie)

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —(CH₂)_(n)—R⁴,    -   —(CH₂)_(l)—S—R⁴,    -   —(CH₂)_(l)—O—R⁴, or    -   —(CH₂)_(l)—N(R^(7b))—R⁴;

-   n is 0, 1 or 2;

-   l is 1 or 2;

-   R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R^(7b) is H, methyl, or ethyl;

-   Ring C is a 3-8 membered carbocycle;    -   wherein said 3-8 membered carbocyclic moiety is saturated or        partially saturated;    -   wherein said 3-8 membered carbocyclic moiety is substituted with        0-3 R²¹;    -   optionally, the carbocycle contains a heteroatom selected from        —O— and —N(R²⁰)—;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,    OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹¹, at each occurrence, is independently selected from H, ═O,    NR¹⁸R¹⁹, CF₃;    -   C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); and    -   5 to 7 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7        membered heterocycle is substituted with 0-3 R^(11b); wherein        said 5 to 7 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, homopiperidinyl, and tetrazolyl;

-   R^(11a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3    R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   W is a bond, —CH₂—, —CH₂CH₂—;

-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—,    —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆    cycloalkyl;

-   R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;

-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄    alkyl)-S(═O)₂—;

-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;

-   R¹⁹, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl; and

-   R²⁰ is H or C₁-C₄ alkyl.

[13] In another preferred embodiment the present invention provides acompound of Formula (Id) and (Ie) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

-   R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from is H, OH,    F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-6 membered carbocycle;    -   wherein said 3-6 membered carbocyclic moiety is saturated or        partially unsaturated;    -   wherein said 3-6 membered carbocyclic moiety is substituted with        0-2 R²¹;    -   optionally, the carbocycle contains a heteroatom selected from        —O— and —N(R²⁰)—;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy,    ethoxy, allyl, —OCF₃, and —SCF₃;

-   R¹¹, at each occurrence, is independently selected from H, ═O,    NR¹⁸R¹⁹, CF₃;    -   C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); and    -   5 to 7 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7        membered heterocycle is substituted with 0-3 R^(11b); wherein        said 5 to 7 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, homopiperidinyl, and tetrazolyl;

-   R^(11a), at each occurrence, is independently selected from H,    methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F,    Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   W is a bond, —CH₂—, —CH₂CH₂—;

-   X is a bond;    -   phenyl substituted with 0-1 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-1 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-1 R^(Xb);

-   R^(Xb) is selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, methoxy, ethoxy,    propoxy, and —OCF₃;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹³, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, and CF₃;

-   R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;

-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, benzyl, and phenethyl;

-   R¹⁶, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,    ethyl-C(═O)—, methyl-S(═O)₂—, and ethyl-S(═O)₂—;

-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

-   R¹⁹, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl;

-   R²⁰ is H or C₁-C₄ alkyl.

[14] In another preferred embodiment the present invention provides acompound of Formula (Id) and (Ie) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

-   R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a), or    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a);

-   R^(4a), at each occurrence, is independently selected from is H, OH,    F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b); wherein        said 5 to 6 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, and tetrazolyl;

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-6 membered carbocycle selected from:

-   -   wherein said 3-6 membered carbocycle is substituted with 0-1        R²¹;

-   R²¹ is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy,    ethoxy, allyl, and —OCF₃;

-   R¹¹, at each occurrence, is independently selected from H, ═O,    NR¹⁸R¹⁹;    -   C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   5 to 7 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7        membered heterocycle is substituted with 0-3 R^(11b); wherein        said 5 to 7 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, homopiperidinyl, and tetrazolyl;

-   R^(11a), at each occurrence, is independently selected from H,    methyl, ethyl, propyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ═O,    NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   W is a bond or —CH₂—;

-   X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 membered    heterocycle;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;    -   phenyl substituted with 0-4 R^(12b);    -   C₃₋₆ carbocycle substituted with 0-4 R^(12b); or    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;

-   R¹³, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN,    NR¹⁵R¹⁶, and CF₃;

-   R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl; and

-   R¹⁶, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, benzyl, and phenethyl.

-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

-   R¹⁹, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl; and

-   R²⁰ is H, methyl, or ethyl.

[15] In another preferred embodiment the present invention provides acompound of Formula (Id) and (Ie) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   Ring C is selected from:

-   R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,    —CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃,    —CH₂CF₃, —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂,    —CH(OH)CH(CH₃)₂, —CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃,    —CF₂CH₂CH(CH₃)₂, —CH(NHCH₃)CH₂CH(CH₃)₂,    —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-, cyclopentyl-,    cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,    cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,    cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,    1—NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,    (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,    (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,    (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,    (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,    (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,    (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,    (3-Cl—F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,    phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;-   W is a bond or —CH₂—;-   X is a bond;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,    t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl,    2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl,    2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl,    3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl,    2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl,    3-F-5-Cl-phenyl, 3-Cl—F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl,    4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl,    3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl,    4-CF₃O-phenyl, furanyl, thienyl, pyridyl, 2-Me-pyridyl,    3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl,    1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,    morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,    (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—,    (3-Cl-phenyl)CH₂, (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—,    (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—,    (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—,    (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—,    (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—,    (3-F-5-Cl-phenyl)CH₂—, (3-Cl—F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—,    (3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—,    (3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—,    (3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—,    (3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—,    (thienyl)CH₂—, (pyridyl)CH₂—, (2-Me-pyridyl)CH₂—,    (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—, (1-imidazolyl)CH₂—,    (oxazolyl)CH₂—, (isoxazolyl)CH₂—, (1-benzimidazolyl)CH₂—,    (cyclopropyl)CH₂—, (cyclobutyl)CH₂—, (cyclopentyl)CH₂—,    (cyclohexyl)CH₂—, (morpholino)CH₂—, (N-piperidinyl)CH₂—,    phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, (3-Cl—F-phenyl)CH₂CH₂—,    (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—, (4-MeO-phenyl)CH₂CH₂—,    (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—, (4-Me-phenyl)CH₂CH₂—,    (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—, (4-MeS-phenyl)CH₂CH₂—,    (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,    (4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,    (pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,    (4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,    (isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,    (cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,    (morpholino)CH₂CH₂—, or (N-piperidinyl)CH₂CH₂—;-   R¹¹, at each occurrence, is independently selected from H, ═O,    methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 3-F-phenyl, (3-F-phenyl)CH₂—,    (3-F-phenyl)CH₂CH₂—, 2-F-phenyl, (2-F-phenyl)CH₂—,    (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,    (4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,    (3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,    (4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,    (3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,    (4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, or    pyrid-4-yl; and-   R¹³, at each occurrence, is independently selected from H, F, Cl,    OH, —CH₃, —CH₂CH₃, —OCH₃, or —CF₃.

[16] In another preferred embodiment the present invention provides acompound of Formula (If):

or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof,wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —(CH₂)_(n)—R⁴,    -   —(CH₂)_(l)—S—R⁴,    -   —(CH₂)_(l)—O—R⁴, or    -   —(CH₂)_(l)—N(R^(7b))—R⁴;

-   n is 0, 1 or 2;

-   l is 1 or 2;

-   R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₈ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from H, OH, F,    Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R^(7b) is H, methyl, or ethyl;

-   Ring C is a 3-8 membered carbocycle;    -   wherein said 3-8 membered carbocyclic moiety is saturated or        partially saturated;    -   wherein said 3-8 membered carbocyclic moiety is substituted with        0-3 R²¹;    -   optionally, the carbocycle contains a heteroatom selected from        —O— and —N(R²⁰)—;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶,    OR^(14a), C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹¹ is selected from    -   H, ═O, NR¹⁸R¹⁹, CF₃;    -   C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); and    -   5 to 7 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7        membered heterocycle is substituted with 0-3 R^(11b); wherein        said 5 to 7 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, homopiperidinyl, and tetrazolyl;

-   R^(11a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3    R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   W is a bond, —CH₂—, —CH₂CH₂—;

-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);

-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—NR^(19b)S(═O)₂—, S(═O)₂NR^(19b)—,    —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆    cycloalkyl;

-   R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;

-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;

-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄    alkyl)-S(═O)₂—;

-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆    alkyl)-S(═O)₂—;

-   R¹⁹, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl; and

-   R²⁰ is H or C₁-C₄ alkyl.

[17] In another preferred embodiment the present invention provides acompound of Formula (If) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

-   R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4a), at each occurrence, is independently selected from is H, OH,    F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b);

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-6 membered carbocycle;    -   wherein said 3-6 membered carbocyclic moiety is saturated or        partially unsaturated;    -   wherein said 3-6 membered carbocyclic moiety is substituted with        0-2 R²¹;    -   optionally, the carbocycle contains a heteroatom selected from        —O— and —N(R²⁰)—;

-   R²¹, at each occurrence, is independently selected from H, OH, Cl,    F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy,    ethoxy, allyl, —OCF₃, and —SCF₃;

-   R¹¹ is selected from    -   H, ═O, NR¹⁸R¹⁹, CF₃;    -   C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); and    -   5 to 7 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7        membered heterocycle is substituted with 0-3 R^(11b); wherein        said 5 to 7 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, homopiperidinyl, and tetrazolyl;

-   R^(11a), at each occurrence, is independently selected from H,    methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F,    Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   W is a bond, —CH₂—, —CH₂CH₂—;

-   X is a bond;    -   phenyl substituted with 0-1 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-1 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-1 R^(Xb);

-   R^(Xb) is selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, methoxy, ethoxy,    propoxy, and —OCF₃;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,    S(═O)CH₃, S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;

-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, benzyl, and phenethyl;

-   R¹⁶, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C(═O)—,    ethyl-C(═O)—, methyl-S(═O)₂—, and ethyl-S(═O)₂—;

-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

-   R¹⁹, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl;

-   R²⁰ is H or C₁-C₄ alkyl.

[18] In another preferred embodiment the present invention provides acompound of Formula (If) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴, —CH₂OR⁴, or —CH₂CH₂OR⁴;

-   R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a), or    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a);

-   R^(4a), at each occurrence, is independently selected from is H, OH,    F, Cl, Br, I, NR¹⁵R¹⁶, CF₃,    -   C₃-C₆ carbocycle substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle containing 1 to 3 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(4b); wherein        said 5 to 6 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, and tetrazolyl;

-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃,    -   C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl,    -   C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;

-   Ring C is a 3-6 membered carbocycle selected from:

-   -   wherein said 3-6 membered carbocycle is substituted with 0-1        R²¹;

-   R²¹ is selected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy,    ethoxy, allyl, and —OCF₃;

-   R¹¹ is selected from    -   H, ═O, NR¹⁸R¹⁹;    -   C₁-C₄ alkyl optionally substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   5 to 7 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7        membered heterocycle is substituted with 0-3 R^(11b); wherein        said 5 to 7 membered heterocycle is selected from pyridinyl,        pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl,        piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,        isoxazolyl, homopiperidinyl, and tetrazolyl;

-   R^(11a), at each occurrence, is independently selected from H,    methyl, ethyl, propyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ═O,    NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b);

-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;

-   W is a bond or —CH₂—;

-   X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 membered    heterocycle;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—;

-   Z is H;    -   C₁-C₈ alkyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(12a);    -   C₂-C₆ alkynyl substituted with 0-3 R^(12a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to        10 membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12a), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;    -   phenyl substituted with 0-4 R^(12b);    -   C₃-6 carbocycle substituted with 0-4 R^(12b); or    -   5 to 6 membered heterocycle containing 1 to 4 heteroatoms        selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6        membered heterocycle is substituted with 0-3 R^(12b);

-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;

-   R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;

-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl; and

-   R¹⁶, at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, benzyl, and phenethyl.

-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;

-   R¹⁹, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl; and

-   R²⁰ is H, methyl, or ethyl.

[19] In another preferred embodiment the present invention provides acompound of Formula (If) wherein:

-   -   L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—;

-   Ring C is selected from:

-   R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,    —CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃,    —CH₂CF₃, —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂,    —CH(OH)CH(CH₃)₂, —CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃,    —CF₂CH₂CH(CH₃)₂, —CH(NHCH₃)CH₂CH(CH₃)₂,    —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-, cyclopentyl-,    cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,    cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,    cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,    1—NH₂-cyclopentyl, phenyl-CH₂—, (2,3-diCl-phenyl)CH₂—,    (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—,    (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—,    (3-F-5-Cl-phenyl)CH₂—, (3-Cl—F-phenyl)CH₂—, phenyl-CH₂CH₂—,    (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,    (2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,    (2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,    (2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,    (3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,    (2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,    (2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,    (3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,    (3-F-4-Cl-phenyl)CH₂CH₂—, (2-F-5-Cl-phenyl)CH₂CH₂—,    4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—, phenyl-CH₂CH(OH)—,    imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—;-   W is a bond or —CH₂—;-   X is a bond;

-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,    t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl,    2-Cl-phenyl, 3-Cl-phenyl,-   Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,    t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl,    2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl,    2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl,    3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl,    2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl,    3-F-5-Cl-phenyl, 3-Cl—F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl,    4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl,    3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl,    4-CF₃O-phenyl, furanyl, thienyl, pyridyl, 2-Me-pyridyl,    3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl,    1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,    morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,    (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—,    (3-Cl-phenyl)CH₂, (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—,    (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—,    (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—,    (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—,    (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—,    (3-F-5-Cl-phenyl)CH₂—, (3-Cl—F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—,    (3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—,    (3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—,    (3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—,    (3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—,    (thienyl)CH₂—, (pyridyl)CH₂—, (2-Me-pyridyl)CH₂—,    (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—, (1-imidazolyl)CH₂—,    (oxazolyl)CH₂—, (isoxazolyl)CH₂—, (1-benzimidazolyl)CH₂—,    (cyclopropyl)CH₂—, (cyclobutyl)CH₂—, (cyclopentyl)CH₂—,    (cyclohexyl)CH₂—, (morpholino)CH₂—, (N-piperidinyl)CH₂—,    phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, (3-Cl—F-phenyl)CH₂CH₂—,    (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—, (4-MeO-phenyl)CH₂CH₂—,    (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—, (4-Me-phenyl)CH₂CH₂—,    (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—, (4-MeS-phenyl)CH₂CH₂—,    (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,    (4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,    (pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,    (4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,    (isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,    (cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,    (morpholino)CH₂CH₂—, or (N-piperidinyl)CH₂CH₂—; and-   R¹¹, at each occurrence, is independently selected from H, ═O,    methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 3-F-phenyl, (3-F-phenyl)CH₂—,    (3-F-phenyl)CH₂CH₂—, 2-F-phenyl, (2-F-phenyl)CH₂—,    (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,    (4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,    (3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,    (4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,    (3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,    (4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, or    pyrid-4-yl.

[20] In another preferred embodiment the present invention provides acompound of Formula (I) selected from:

-   {[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carboxamide;-   {[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide;-   [(N-butylcarbamoyl)cyclopentyl]-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide;-   2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}acetamide;-   2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}acetamide;-   2-(3,5-difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopropyl}acetamide;-   3-cyclopentyl-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}propanamide;-   2-(3,5-difluorophenyl)-N-{4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl](4-piperidyl)}acetamide;-   phenyl    4-[2-(3,5-difluorophenyl)acetylamino]-4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]piperidinecarboxylate;-   4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;-   N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}{[(phenylmethoxy)carbonylamino]cyclopentyl}carboxamide;-   (2S)-N-{[N-(1-{[3-(4-fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopropyl}-2-hydroxy-4-methylpentanamide;-   (2S)-N-{[N-(1-{[3-(4-fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopentyl}-2-hydroxy-3-methylbutanamide;-   2,2-difluoro-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-4-phenylbutanamide;-   N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-(4-piperidyl)propanamide;-   (2S)-2-hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;-   3-cyclopropyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;-   (2R)-2-hydroxy-3-imidazol-2-yl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;-   2-ethoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;-   3-cyclopentyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;-   (2S)-2-hydroxy-3-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]butanamide;-   (2S)-2-cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;-   (2R)-2-cyclohexyl-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide;-   (2S)-2-amino-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;-   [(cyclohexylcarbonylamino)cyclopentyl]-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide;-   {[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide;-   4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;-   (2S)-2-hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide;-   3-methoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide;-   (2S)-2-hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-phenylpropanamide;-   N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-2-(phenylmethoxy)acetamide;-   (2S)-2-hydroxy-3-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}butanamide;-   (2S)-2-hydroxy-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;-   3-cyclopentyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide;-   (2S)-2-cyclohexyl-2-hydroxy-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}acetamide;-   3-cyclopropyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide;-   N-{[N-(1-butyl-5-cyclopentyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;-   N-{[N-(5-cyclopentyl-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;-   (2S)-2-hydroxy-3-methyl-N-({N-[2-oxo-1-benzyl(3H,4H,5H-benzo[f]azaperhydroepin-3-yl)]carbamoyl}cyclopentyl)butanamide;-   (2S)-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-2-[(propylsulfonyl)amino]pentanamide;-   (2S)-2-amino-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;-   2,2-difluoro-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;-   4-methyl-N-{[N-(6-oxo(5H,7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide;-   N-({N-[5-(3,3-dimethyl-2-oxobutyl)-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;-   4-methyl-N-[(N-{6-oxo-5-[(3-phenoxyphenyl)methyl](7H-dibenzo[d,f]azaperhydroepin-7-yl)}carbamoyl)cyclopentyl]pentanamide;-   N-{[N-(5-butyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-4-methylpentanamide;-   4-methyl-N-({N-[6-oxo-5-benzyl(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)pentanamide;-   N-({N-[5-(tert-butyl)-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;-   N-({N-[5-(tert-butyl)-1-butyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide;    and-   N-({N-[5-butyl-2-oxo-1-(2-pyridylmethyl)(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide.

In another embodiment the present invention provides for a method forthe treatment of neurological disorders associated with β-amyloidproduction comprising administering to a host in need of such treatmenta therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt or prodrug thereof.

It is understood that any and all embodiments of the present inventionmay be taken in conjunction with any other embodiment to describeadditional even more preferred embodiments of the present invention.

In a second embodiment, the present invention provides a pharmaceuticalcomposition comprising a compound of Formula (I) and a pharmaceuticallyacceptable carrier.

In a third embodiment, the present invention provides a method for thetreatment of neurological disorders associated with β-amyloid productioncomprising administering to a host in need of such treatment atherapeutically effective amount of a compound of Formula (I).

In a preferred embodiment the neurological disorder associated withβ-amyloid production is Alzheimer's Disease.

In a fourth embodiment, the present invention provides a method forinhibiting γ-secretase activity for the treatment of a physiologicaldisorder associated with inhibiting γ-secretase activity comprisingadministering to a host in need of such inhibition a therapeuticallyeffective amount of a compound of Formula (I) that inhibits γ-secretaseactivity.

Thus, the present invention provides a method for inhibiting γ-secretaseactivity comprising administering to a host in need of such inhibition atherapeutically effective amount of a compound of Formula (I) thatinhibits γ-secretase activity.

In a preferred embodiment the physiological disorder associated withinhibiting γ-secretase activity is Alzheimer's Disease.

In a fifth embodiment, the present invention provides a compound ofFormula (I) for use in therapy.

In a preferred embodiment the present invention provides a compound ofFormula (I) for use in therapy of Alzheimer's Disease.

In a sixth embodiment, the present invention provides for the use of acompound of Formula (I) for the manufacture of a medicament for thetreatment of Alzheimer's Disease.

It is understood that any and all embodiments of the present inventionmay be taken in conjunction with any other embodiment to describeadditional even more preferred embodiments of the present invention.

DEFINITIONS

As used herein, the term “Aβ” denotes the protein designated Aβ,β-amyloid peptide, and sometimes β/A4, in the art. Aβ is anapproximately 4.2 kilodalton (kD) protein of about 39 to 43 amino acidsfound in amyloid plaques, the walls of meningeal and parenchymalarterioles, small arteries, capillaries, and sometimes, venules. Theisolation and sequence data for the first 28 amino acids are describedin U.S. Pat. No. 4,666,829. The 43 amino acid sequence is:

1 Asp Ala Glu Phe Arg His Asp Ser Gly Tyr 11 Glu Val His His Gln Lys LeuVal Phe Phe 21 Ala Glu Asp Val Gly Ser Asn Lys Gly Ala 31 Ile Ile GlyLeu Met Val Gly Gly Val Val 41 Ile Ala Thr

The term “APP”, as used herein, refers to the protein known in the artas β amyloid precursor protein. This protein is the precursor for Aβ andthrough the activity of “secretase” enzymes, as used herein, it isprocessed into Aβ. Differing secretase enzymes, known in the art, havebeen designated β secretase, generating the N-terminus of Aβ, αsecretase cleaving around the 16/17 peptide bond in Aβ, and “γsecretases”, as used herein, generating C-terminal Aβ fragments endingat position 38, 39, 40, 42, and 43 or generating C-terminal extendedprecursors which are subsequently truncated to the above polypeptides.

The compounds herein described may have asymmetric centers. Compounds ofthe present invention containing an asymmetrically substituted atom maybe isolated in optically active or racemic forms. It is well known inthe art how to prepare optically active forms, such as by resolution ofracemic forms or by synthesis from optically active starting materials.Many geometric isomers of olefins, C═N double bonds, and the like canalso be present in the compounds described herein, and all such stableisomers are contemplated in the present invention. Cis and transgeometric isomers of the compounds of the present invention aredescribed and may be isolated as a mixture of isomers or as separatedisomeric forms. All chiral, diastereomeric, racemic forms and allgeometric isomeric forms of a structure are intended, unless thespecific stereochemistry or isomeric form is specifically indicated.

The term “substituted,” as used herein, means that any one or morehydrogens on the designated atom is replaced with a selection from theindicated group, provided that the designated atom's normal valency isnot exceeded, and that the substitution results in a stable compound.When a substituent is keto (i.e., ═O), then 2 hydrogens on the atom arereplaced.

When any variable (e.g., R^(5b)) occurs more than one time in anyconstituent or formula for a compound, its definition at each occurrenceis independent of its definition at every other occurrence. Thus, forexample, if a group is shown to be substituted with 0-2 R^(5b), thensaid group may optionally be substituted with up to two R^(5b) groupsand R^(5b) at each occurrence is selected independently from thedefinition of R^(5b). Also, combinations of substituents and/orvariables are permissible only if such combinations result in stablecompounds.

When a bond to a substituent is shown to cross a bond connecting twoatoms in a ring, then such substituent may be bonded to any atom on thering. When a substituent is listed without indicating the atom via whichsuch substituent is bonded to the rest of the compound of a givenformula, then such substituent may be bonded via any atom in suchsubstituent. Combinations of substituents and/or variables arepermissible only if such combinations result in stable compounds.

As used herein, “alkyl” or “alkylene” is intended to include bothbranched and straight-chain saturated aliphatic hydrocarbon groupshaving the specified number of carbon atoms; for example, “C₁-C₆ alkyl”denotes alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms. Examples of alkylinclude, but are not limited to, methyl, ethyl, n-propyl, i-propyl,n-butyl, i-butyl, sec-butyl, t-butyl, pentyl, and hexyl. Preferred“alkyl” group, unless otherwise specified, is “C₁-C₄ alkyl”.Additionally, unless otherwise specified, “propyl” denotes n-propyl ori-propyl; “butyl” denotes n-butyl, i-butyl, sec-butyl, or t-butyl.

As used herein, “alkenyl” or “alkenylene” is intended to includehydrocarbon chains of either a straight or branched configuration andone or more unsaturated carbon-carbon bonds which may occur in anystable point along the chain. Examples of “C₂-C₆ alkenyl” include, butare not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-butenyl,2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 2-pentenyl, 3-pentenyl,hexenyl, and the like.

As used herein, “alkynyl” or “alkynylene” is intended to includehydrocarbon chains of either a straight or branched configuration andone or more carbon-carbon triple bonds which may occur in any stablepoint along the chain, such as ethynyl, 1-propynyl, 2-propynyl,1-butynyl, 2-butynyl, 3-butynyl, and the like.

“Alkoxy” or “alkyloxy” represents an alkyl group as defined above withthe indicated number of carbon atoms attached through an oxygen bridge.Examples of alkoxy include, but are not limited to, methoxy, ethoxy,n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, ands-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n-propoxy,i-propoxy, n-butoxy, s-butoxy, t-butoxy. Similarly, “alkylthio” or“thioalkoxy” is represents an alkyl group as defined above with theindicated number of carbon atoms attached through a sulphur bridge.

“Halo” or “halogen” as used herein refers to fluoro, chloro, bromo, andiodo. Unless otherwise specified, preferred halo is fluoro and chloro.“Counterion” is used to represent a small, negatively charged speciessuch as chloride, bromide, hydroxide, acetate, sulfate, and the like.

“Haloalkyl” is intended to include both branched and straight-chainsaturated aliphatic hydrocarbon groups having the specified number ofcarbon atoms, substituted with 1 or more halogen (for example—C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)). Examples of haloalkylinclude, but are not limited to, trifluoromethyl, trichloromethyl,pentafluoroethyl, pentachloroethyl, 2,2,2-trifluoroethyl,2,2-difluoroethyl, heptafluoropropyl, and heptachloropropyl.“Haloalkoxy” is intended to mean a haloalkyl group as defined above withthe indicated number of carbon atoms attached through an oxygen bridge;for example trifluoromethoxy, pentafluoroethoxy, 2,2,2-trifluoroethoxy,and the like. “Halothioalkoxy” is intended to mean a haloalkyl group asdefined above with the indicated number of carbon atoms attached througha sulphur bridge.

“Cycloalkyl” is intended to include saturated ring groups, having thespecified number of carbon atoms. For example, “C₃-C₆ cycloalkyl”denotes such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

As used herein, “carbocycle” is intended to mean any stable 3- to7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic ortricyclic, any of which may be saturated, partially unsaturated, oraromatic. Examples of such carbocycles include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane,[4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl,naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin).Preferred “carbocycle” are cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

As used herein, the term “heterocycle” or “heterocyclic ring” isintended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7-to 14-membered bicyclic heterocyclic ring which is saturated partiallyunsaturated or unsaturated (aromatic), and which consists of carbonatoms and 1, 2, 3 or 4 heteroatoms independently selected from the groupconsisting of N, O and S and including any bicyclic group in which anyof the above-defined heterocyclic rings is fused to a benzene ring. Thenitrogen and sulfur heteroatoms may optionally be oxidized. Theheterocyclic ring may be attached to its pendant group at any heteroatomor carbon atom which results in a stable structure. The heterocyclicrings described herein may be substituted on carbon or on a nitrogenatom if the resulting compound is stable. If specifically noted, anitrogen in the heterocycle may optionally be quaternized. It ispreferred that when the total number of S and O atoms in the heterocycleexceeds 1, then these heteroatoms are not adjacent to one another. It ispreferred that the total number of S and O atoms in the heterocycle isnot more than 1.

Examples of heterocycles include, but are not limited to, 1H-indazole,2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl,4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl,acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl,carbazolyl, 4aH-carbazolyl, b-carbolinyl, chromanyl, chromenyl,cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl,imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl,indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl,isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinylperimidinyl,phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl,phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl,piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl,purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl,pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl,pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl,quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl,tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl,6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl,thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl,triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl, xanthenyl. Preferred 5 to 10 membered heterocyclesinclude, but are not limited to, pyridinyl, pyrimidinyl, triazinyl,furanyl, thienyl, thiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl,isoxazolyl, tetrazolyl, benzofuranyl, benzothiofuranyl, indolyl,benzimidazolyl, 1H-indazolyl, oxazolidinyl, isoxazolidinyl,benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, quinolinyl,and isoquinolinyl. Preferred 5 to 6 membered heterocycles include, butare not limited to, pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, tetrazolyl; more preferred 5 to 6 memberedheterocycles include, but are not limited to, pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, piperazinyl, piperidinyl,pyrazolyl, imidazolyl, and tetrazolyl. Also included are fused ring andspiro compounds containing, for example, the above heterocycles.

As used herein, the term “aryl”, “C₆-C₁₀ aryl” or aromatic residue, isintended to mean an aromatic moiety containing the specified number ofcarbon atoms; for example phenyl, pyridinyl or naphthyl. Preferred“aryl” is phenyl. Unless otherwise specified, “aryl” may beunsubstituted or substituted with 0 to 3 groups selected from H, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, amino, hydroxy,Cl, F, Br, I, CF₃, SCH₃, S(O)CH₃, SO₂CH₃, —N(CH₃)₂, N(CH₃)H, CN, NO₂,OCF₃, C(═O)CH₃, CO₂H, CO₂CH₃, or C₁-C₄ haloalkyl.

The phrase “additional lactam carbons”, as used herein, is intended todenote the number of optional carbon atoms in the lactam ring B ofFormula (I). Formula (I″):

represents the lactam ring B of Formula (I). Additional lactam carbonsare carbons in lactam ring B other than the carbons numbered 2 and 3 inthe backbone of the formula. The additional lactam carbons may beoptionally replaced by a heteroatom selected from oxygen, nitrogen andsulfur. Lactam ring B contains 1, 2, 3, 4, 5, 6 or 7 optional carbons,wherein one optional carbon may optionally be replaced by a heteroatom,such that the total number of members of lactam ring B, including atomsnumbered 1, 2 and 3 in the backbone, does not exceed 10. It is preferredthat the total number of atoms of lactam ring B is 6, 7 or 8; it is morepreferred that the total number of atoms of lactam ring B is seven. Itis further understood that lactam ring B may optionally be unsaturatedor partially unsaturated (i.e. two adjacent atoms in the ring form adouble bond) wherein the backbone of lactam ring B may contain one, twoor three double bonds. Examples of lactam ring B include:

but are not intended to limit the invention. Preferred examples oflactam ring B are B1, B2, B5, B6, B8, B9, B13, and B16; more preferredexamples of lactam ring B are B1, B6, B8, B9, and B13. Preferredexamples of substituent R¹⁰ or R¹¹ on lactam B are methyl, ethyl,phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-trifluoromethylphenyl,(4-fluorophenyl)methyl, (4-chlorophenyl)methyl,(4-trifluoromethylphenyl)methyl, and 2-, 3-, and 4-pyridinyl. Preferredexamples of R¹³ on lactam B are F, Cl, OH, methyl, ethyl, methoxy, andtrifluoromethyl.

The compounds herein described may have asymmetric centers. Oneenantiomer of a compound of Formula (I) may display superior biologicalactivity over the opposite enantiomer. For example carbon 3 of lactamring B Formula (I″) may exist in either an S or R configuration. Thus,an R or S configuration at carbon 3 in Formula (I″) is considered partof the invention. An example of such configuration includes,

but is not intended to be limited to this example of ring B. Whenrequired, separation of the racemic material can be achieved by methodsknown in the art.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

As used herein, “pharmaceutically acceptable salts” refer to derivativesof the disclosed compounds wherein the parent compound is modified bymaking acid or base salts thereof. Examples of pharmaceuticallyacceptable salts include, but are not limited to, mineral or organicacid salts of basic residues such as amines; alkali or organic salts ofacidic residues such as carboxylic acids; and the like. Thepharmaceutically acceptable salts include the conventional non-toxicsalts or the quaternary ammonium salts of the parent compound formed,for example, from non-toxic inorganic or organic acids. For example,such conventional non-toxic salts include those derived from inorganicacids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric,nitric and the like; and the salts prepared from organic acids such asacetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric,citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic,benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric,toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic,and the like.

The pharmaceutically acceptable salts of the present invention can besynthesized from the parent compound which contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two; generally, nonaqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare preferred. Lists of suitable salts are found in Remington'sPharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa.,1985, p. 1418, the disclosure of which is hereby incorporated byreference.

“Prodrugs” are intended to include any covalently bonded carriers whichrelease the active parent drug according to formula (I) in vivo whensuch prodrug is administered to a mammalian subject. Prodrugs of acompound of formula (I) are prepared by modifying functional groupspresent in the compound in such a way that the modifications arecleaved, either in routine manipulation or in vivo, to the parentcompound. Prodrugs include compounds of formula (I) wherein a hydroxy,amino, or sulfhydryl group is bonded to any group that, when the prodrugor compound of formula (I) is administered to a mammalian subject,cleaves to form a free hydroxyl, free amino, or free sulfhydryl group,respectively. Examples of prodrugs include, but are not limited to,acetate, formate and benzoate derivatives of alcohol and aminefunctional groups in the compounds of formula (I), and the like.

“Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent.

SYNTHESIS

The compounds of the present invention can be prepared in a number ofways well known to one skilled in the art of organic synthesis. Thecompounds of the present invention can be synthesized using the methodsdescribed below, together with synthetic methods known in the art ofsynthetic organic chemistry, or variations thereon as appreciated bythose skilled in the art. Preferred methods include, but are not limitedto, those described below. All references cited herein are herebyincorporated in their entirety herein by reference.

The novel compounds of this invention may be prepared using thereactions and techniques described in this section. The reactions areperformed in solvents appropriate to the reagents and materials employedand which are suitable for the transformations being effected. Also, inthe description of the synthetic methods described below, it is to beunderstood that all proposed reaction conditions, including choice ofsolvent, reaction atmosphere, reaction temperature, duration of theexperiment and work-up procedures, are chosen to be the conditionsstandard for that reaction, which should be readily recognized by oneskilled in the art. It is understood by one skilled in the art oforganic synthesis that the functionality present on various portions ofthe molecule must be compatible with the reagents and reactionsproposed. Such restrictions to the substituents which are compatiblewith the reaction conditions will be readily apparent to one skilled inthe art and alternate methods must then be used.

In a preferred method of synthesis, the compounds of Formula (I) of thepresent invention can be prepared from carboxylic acid 1 and amine 2using amide bond syntheses known in the art, including methods commonlyused in peptide syntheses, such as HATU, TBTU, BOP, EDC, CDI, andDCC-mediated couplings, as illustrated in Scheme 1. Depending on thestructure of the final product, it is appreciated by those skilled inthe art that protecting groups or precursor functionality convertible tothe desired groups may be desirable. Protecting groups and their use insynthesis are described in Green and Wuts, Protective Groups in OrganicSynthesis, (Wiley 1991).

Additionally, the syntheses of a representative malonamide and arepresentative acetamide of Formula (I) are illustrated in Scheme 2 andScheme 3, respectively. As will be readily apparent to those of ordinaryskill in the art, the synthetic procedure illustrated in Scheme 2 and 3,and the reaction conditions described below can be modified by selectingthe appropriate starting materials and reagents to allow the preparationof other compounds of the present invention.

Methods for the synthesis of lactams useful as intermediates in thesynthesis of compounds of the present invention, including aminobisbenzodiazepine 5 and amino benzodiazepine 8, are known in the art andare disclosed in a number of references including PCT publication numberWO 98/28268, WO 99/66934, and WO00/07995, which are hereby incorporatedby reference. Additional references include Bock, et. al., J. Org.Chem., 1987, 52, 3232-3239; Sherrill et. al., J. Org. Chem., 1995, 60,730-734; Walsh, D. A., Synthesis, September 1980, p. 677; and Brown, at.al., Tetrahedron Letters, 1971, 8, 667-670.

Cyclic carboxylic acid intermediates, such as 4, are useful for thesynthesis of the current invention, and may be synthesized by a numberof ways well known in the art. One of the preferred syntheses of thecompounds of this invention is shown in Scheme 4. Typically a convergentroute is employed, which joins the acid 11 and the amine together toafford the key intermediate 12 using standard bond-forming procedures(Synthesis 1989, 37-38). The desired carboxylic acid 4 may be preparedfrom the known malonate ester 10 (e.g. Chung, S. K. Korean J. Med. Chem.1995, 5, 94-111) via a three-step protocol as shown in Scheme 4.

One of the preferred syntheses of cyclic amino acids, such as 7 which isuseful in the preparation of compounds of Formula (I), is outlined inScheme 5. As illustrated for the synthesis of carboxylic acid 7, thedesired intermediate ester 18 is prepared by the initial couplingreaction of acid 14 and amine 13 under standard conditions using EDC andHOBt. Both the acids and the amines employed as starting materials inthis invention are either commercially available or can be prepared fromcommercially available materials using conventional procedures andreagents. As apparent to those of ordinary skill in the art, thesynthetic procedure illustrated in Scheme 5 and the reaction conditionsdescribed will allow the preparation of many other analogs of 7 byselecting the appropriate starting materials and reagents.

Methods for the synthesis of lactams useful as intermediates in thesynthesis of compounds of the present invention are known in the art andare disclosed in a number of references including PCT publication numberWO 98/28268, WO 99/66934, and WO00/07995, which are hereby incorporatedby reference. Additional references include Bock, et. al., J. Org.Chem., 1987, 52, 3232-3239; Sherrill et. al., J. Org. Chem., 1995, 60,730-734; Walsh, D. A., Synthesis, September 1980, p. 677; and Brown, at.al., Tetrahedron Letters, 1971, 8, 667-670.

One of the preferred syntheses of the lactam intermediates, such as 23,is outlined in Scheme 6.

a) Preparation of 21

To a suspension of 19 (30.0 g, 155 mmol) in dry Et₂O (300 mL) under N₂at −70° C. was added t-BuLi (205 mL, 1.7 M in pentane) and stirred for 4h between −20° C. and −10° C. The reaction was cooled to −70° C. andtransferred via canula to a round bottom containing 20 (23.0 mL, 186mmol) in dry Et₂O (150 mL) under N₂ at −70° C. The reaction was stirredwhile warming to rt for 14 h and quenched with 20% citric acid. Theresulting layers were separated and the organic layer was washed withsat. NaHCO₃, brine, dried over Na₂SO₄, filtered and concentrated to givea yellow oil. The oil was dissolved in EtOH-HCl (200 mL) and stirredovernight. The solvent was removed in vacuo at 70° C. and the resultingoil triturated with Et₂O. The resultant solid was filtered and washedwith Et₂O to afford 21 HCl (23.9 g, 64%) as a orange solid: ¹H NMR (500MHz, CD₃OD) δ 8.10 (d, 1H), 7.66 (t, 1H), 7.56 (t, 1H), 7.51 (d, 1H),1.41 (s, 9H); ESI MS m/z=178 [C₁₁H₁₅NO+H]⁺.

The orange solid was dissolved in 1N NaOH and EtOAC and the layers wereseparated. The organic layer was washed with brine, dried over Na₂SO₄,filtered and concentrated to afford 21 (21 g, 99%) as a yellow oil: ¹HNMR (500 MHz, CD₃OD) δ 7.70 (d, 1H), 7.16 (t, 1H), 6.78 (d, 1H), 6.59(t, 1H), 1.38 (s, 9H).

b) Preparation of Example 23

To a solution of 22 (5.5 g, 17.0 mmol) in dry THF (50 mL) at 0° C. wasadded oxalyl chloride (1.47 mL, 17.0 mmol) and DMF (0.2 mL) and stirredfor 1.25 h. A solution of 21 (3.3 g, 15.4 mmol) and N-methylmorpholine(4.7 mL, 42.4 mmol) in dry THF (20 mL) was added to the reactiondropwise and the reaction was stirred at rt for 1.5 h. The reaction wasfiltered and MeOH (100 mL) and NH₄OH (50 mL) was added to the filtrateand the reaction was sealed. After 45 min, the reaction was concentratedto half its volume and added dropwise to a cooled solution (15° C.) ofammonium acetate (5.75 g) in acetic acid (120 ml). The reaction wasstirred over night at rt, dissolved in Et₂O (100 mL), made basic with 6N NaOH, and cooled in ice while stirring for 1 h. The resulting solidwas filtered, washed with H₂O and Et₂O, and dried in a vacuum oven at30° C. to afford 23 (3.5 g, 63%) as a white solid: ¹H NMR (500 MHz,CD₃OD) δ 7.78-7.16 (m, 10H), 5.12 (s, 2H), 1.27 (s, 9H).

Abbreviations used in the description of the chemistry and in theexamples that follow are:

Ac acetyl or acetateaq aqueousBn benzylBoc t-butyloxycarbonylCbz benzyloxycarbonylDIEA N,N′-diisopropylethylamineDMAP 4-dimethylaminopyridineDME ethylene glycol dimethyl etherDMF N,N′-dimethylformamideDMSO dimethylsulfoxide or methyl sulfoxideEDC.HCl 1-(3-dimethylaminopropyl)-3-ethylcarbodiimideHOBT 1-hydroxybenzotriazoleHPLC high performance liquid chromatographyLiHMDS lithium hexamethyldisilazideMeCN acetonitrileMS mass spectrometrysatd saturatedrt or RT room temperatureTFA trifluoroacetic acidTHF tetrahydrofuranTLC thin layer chromatography

EXAMPLES

The examples provided are intended to assist in a further understandingof the invention. Particular materials employed, species and conditionsare intended to be further illustrate of the invention and not limit thereasonable scope thereof.

Compounds of the present invention are generally purified by HPLC usingconditions known to one skilled in the art. However, unless otherwiseindicated, the following conditions are generally applicable. HPLCCondition A: reverse-phase HPLC can be carried out using a Vydac C-18column with gradient elution from 10% to 100% buffer B in buffer A(buffer A: water containing 0.1% trifluoroacetic acid, buffer B: 10%water, 90% acetonitrile containing 0.1% trifluoroacetic acid).Alternatively: HPLC Condition B: reverse-phase HPLC can be carried outusing a Vydac C-18 column with gradient elution from 10% to 90%acetonitrile in water.

Example 1{[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carboxamide

(a) Methyl 1-[N-(3-methylbutyl)carbamoyl]cyclopentanecarboxylate

To 1-(methoxycarbonyl)cyclopentanecarboxylic acid (630 mg, 3.7 mmol) inCH₂Cl₂/DMF (5:1, 37 mL) at 0° C. was added HOBT (730 mg, 4.8 mmol) andEDC (920 mg, 4.8 mmol). The mixture was stirred for 10 min then3-methylbutylamine (640 mg, 7.4 mmol) was added and stirring wascontinued for 1 h. The solution was poured into water and the layersseparated. The aqueous layer was extracted with methylene chloride andthe combined extracts were washed with water, 1N HCl, sat'd NaHCO₃,dried over magnesium sulfate, and concentrated to a glassy solid (800mg, 90%). MS [M+H]⁺ 243.

(b) Methyl 1-[N-(3-methylbutyl)carbamoyl]cyclopentanecarboxylic acid

To a solution of methyl1-[N-(3-methylbutyl)carbamoyl]cyclopentanecarboxylate (820 mg, 3.4 mmol)in 25 mL of THF cooled to 0° C. was added dropwise a solution of lithiumhydroxide monohydrate (260 mg, 6.12 mmol) in 5.0 mL of water. Thereaction mixture was stirred at rt for 16 h. THF was removed underreduced pressure to give a yellow oil which was diluted with 10 mL of 1NHCl. The aqueous phase was extracted with CH₂Cl₂ (8×15 mL), and theextracts were combined, dried over Na₂SO₄, and concentrated to afford700 mg (90%) of methyl1-[N-(3-methylbutyl)carbamoyl]-cyclopentanecarboxylic acid as a whitesolid. MS [M+H]⁺ 228.

(c){[N-(3-methylbutyl)carbamoyl]cyclopentyl}-N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carboxamide

To 1-[N-(3-methylbutyl)carbamoyl]cyclopentane carboxylic acid (38 mg,0.16 mmol) in CH₂Cl₂/DMF (5:1, 15 mL) at 0° C. was added HOBT (28 mg,0.18 mmol) and EDC (34 mg, 0.18 mmol). The mixture was stirred for 10min then 7-amino-5-methyl-7H-dibenzoazaperhydroepin-6-one (40 mg, 0.16mmol) (obtained as the first eluting peak of a racemic mixture on aCHIRALCEL OD column with 20% iPrOH/Hexane with diethylamine) was addedand stirring was continued for 1 h. The solution was poured into waterand the layers separated. The aqueous layer was extracted with methylenechloride and the combined extracts were washed with water, 1N HCl, sat'dNaHCO₃, dried over magnesium sulfate, and concentrated to a glassy solid(67 mg, 94%). ¹H NMR (300 MHz, CD₃OD) δ 7.20-7.80 (m, 9H), 6.25 (m, 1H),5.25 (d, 1H), 3.38 (s, 3H), 3.27 (m, 1H), 2.58-2.05 (m, 5H), 1.80-1.25(m, 8H), 0.95, (m, 6H). MS [M+H]⁺ 448.

Example 2{[N-(3-Methylbutyl)carbamoyl]cyclopentyl}-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

The title compound was prepared in a manner similar to that describedfor Example 1. The product was obtained as a solid. MS [M+H]⁺ 475.

Example 3[(N-Butylcarbamoyl)cyclopentyl]-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

The title compound was prepared in a manner similar to that describedfor Example 1. The product was obtained as a solid. MS [M+H]⁺ 461.

Example 42-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}-acetamide

(a){[(tert-Butoxy)carbonylamino]cyclohexyl}-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

Diisopropylethylamine (2.5 mL, 15.0 mmol) and HATU (2.85 g, 7.5 mmol)were added to a solution of1-[(tert-butoxy)carbonylamino]cyclohexanecarboxylic acid (1.75 g, 7.2mmol) in CH₂Cl₂ (10 mL) at 0° C. and stirred for 10 min.(S)-3-amino-1-methyl-5-phenyl-3H-benzoazepin-2-one (3.0 g, 6.0 mmol) wasthen added. The solution was allowed to warm to room temperature andstirred overnight. The reaction was quenched with water. The organiclayer was separated and washed with a saturated solution of NaHCO₃, 20%citric acid, brine, dried over Na₂SO₄, filtered and concentrated toafford a white solid (2.98 g, 99%). This compound underwent no furtherpurification: ¹H NMR (500 MHz, CD₃OD) δ 7.33-7.13 (m, 9H), 5.35 (s, 1H),3.48 (s, 3H), 2.21-1.29 (m, 10H), 1.50, (s, 9H).

(b)(Aminocyclohexyl)-N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carboxamide

A saturated solution of HCl in EtOAc (50 mL) was added to a solution of{[(tert-butoxy)carbonylamino]cyclohexyl}-(S)-3-N-(1-methyl-2-oxo-5-phenyl(3H-benzoazepin-3-yl))carboxamide(2.9 g, 5.9 mmol) in EtOAc (75 mL) and stirred at room temperatureovernight. The reaction was quenched with 1N NaOH (100 mL). The organiclayer was separated, and the aqueous layer was extracted with EtOAc. Theorganic layers were combined, washed with brine, dried over Na₂SO₄,filtered and concentrated to give a white solid (1.76 g, 77%). mp106-110° C.; ¹H NMR (500 MHz, CD₃OD) δ 7.33-7.13 (m, 9H), 5.32 (s, 1H),3.48 (s, 3H), 1.98-1.25 (m, 10H); CI MS m/z=391 [C₂₃H₂₆N₄O₂+H]⁺; HPLC100%, t_(r)=9.17 min. (HPLC Conditions A).

(c)2-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]-cyclohexyl}acetamide

Diisopropylethylamine (0.87 ml, 5.15 mmol) and HATU (979 mg, 2.58 mmol)were added to a solution of 2-(3,5-difluorophenyl)acetic acid (426 mg,2.47 mmol) in CH₂Cl₂ (40 mL) at 0° C. and stirred for 5 min.(Aminocyclohexyl)-(S)-3-N-(1-methyl-2-oxo-5-phenyl(3H-benzoazepin-3-yl))carboxamide(800 mg, 2.06 mmol) was then added, and the solution was allowed to warmto room temperature and stirred overnight. The reaction was quenchedwith water. The organic layer was separated and washed with a saturatedsolution of NaHCO₃, 20% citric acid, brine, dried over Na₂SO₄, filteredand concentrated to give a white solid. Further purification by flashcolumn chromatography afforded the title compound (659 mg, 60%) as awhite solid: mp 126-129° C.; ¹H NMR (500 MHz, CD₃OD) δ 7.72-7.32 (m,9H), 6.97 (d, 2H), 6.80 (t, 1H), 5.31 (s, 1H), 3.70 (s, 2H), 3.48 (s,3H), 2.24-1.30 (m 10H); API MS m/z=545 [C₃₁H₃₀F₂N₄O₃+H]⁺; HPLC 99.5%,t_(r)=22.26 min. (HPLC Conditions A).

Example 52-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-acetamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as a solid. mp 112-117° C.; ¹HNMR (500 MHz, CD₃OD) δ 7.72-7.31 (m, 9H), 6.96 (d, 2H), 6.81 (t, 1H)5.33 (s, 1H), 3.63 (s, 2H), 3.47 (s, 3H), 2.41-1.72 (m, 8H); API MSm/z=531 [C₃₀H₂₈F₂N₄O₃+H]⁺; HPLC 99.4%, t_(r)=21.23 min. (HPLC ConditionsA).

Example 62-(3,5-Difluorophenyl)-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopropyl}-acetamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as a solid. mp 212-214° C.; ¹HNMR (500 MHz, CD₃OD) δ 7.71-7.30 (m, 9H), 6.98 (d, 2H), 6.81 (t, 1H),5.28 (s, 1H), 3.65 (s, 2H), 3.48 (s, 3H), 1.48 (m, 2H), 1.08 (m, 2H);API MS m/z=503 [C₂₈H₂₄F₂N₄O₃+H]⁺; HPLC 97.7%, t_(r)=19.48 min. (HPLCConditions A).

Example 73-Cyclopentyl-N-{[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclohexyl}propanamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as a solid. mp 88-103° C.; ¹HNMR (500 MHz, CD₃OD) δ 7.71-7.30 (m, 9H), 5.28 (d, 1H), 3.51 (d, 3H),2.39-0.82 (m, 23H); CI MS m/z=516 [C₃₁H₃₈N₄O₃+H]⁺; HPLC 96.5%,t_(r)=14.79 min. (HPLC Conditions A).

Example 82-(3,5-Difluorophenyl)-N-{4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl](4-piperidyl)}acetamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as an oil. ¹H NMR (300 MHz,CD₃OD) δ 7.15-7.60 (m, 10H), 6.05-6.80 (m, 3H), 5.40 (d, 1H), 3.60 (s,2H), 3.40 (s, 3H), 2.90 (m, 2H), 2.60 (m, 2H), 2.05, (m, 4H). MS [M+H]⁺546.

Example 9 Phenyl4-[2-(3,5-difluorophenyl)acetylamino]-4-[N-(1-methyl-2-oxo-5-phenyl((S)-3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]piperidinecarboxylate

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as an oil. ¹H NMR (300 MHz,CD₃OD) δ 7.20-7.40 (m, 15H), 6.45-6.80 (m, 3H), 5.40 (d, 1H), 5.15 (s,2H), 4.85 (s, 3H), 3.85 (m, 1H), 3.60 (s, 2H), 3.40 (s, 3H), 2.20, (m,4H). MS [M+H]⁺ 680.

Example 104-Methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4. This compound was made from the amino bisbenzazepineobtained as the first eluting peak of a racemic mixture on a CHIRALCELOD column with 20% iPrOH/Hexane with diethylamine. The product wasobtained as an oil. ¹H NMR (300 MHz, CD₃OD) δ 7.20-7.60 (m, 8H), 6.59(s, 1H), 5.20 (d, 1H), 3.40 (s, 3H), 2.40-1.60 (m, 13H), 0.9, (d, 6H).MS [M+H]⁺ 448.

Example 11N-{1-Methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}{[(phenylmethoxy)carbonylamino]-cyclopentyl}carboxamide

The title compound was prepared in a manner similar to that describedfor Example 4. This compound was made from the corresponding aminobenzodiazepine that, as the CBz protected form, was the first elutingpeak of the racemic mixture on a CHIRALCEL AD column using acetonitrile.The product was obtained as an oil. ¹H NMR (300 MHz, CD₃OD) δ 7.20-7.40(m, 13H), 5.2 (s, 2H), 5.60 (m, 1H), 5.40 (d, 1H), 5.15 (s, 2H), 3.45(s, 3H), 2.40 (m, 2H), 2.05-1.80 (m, 6H). MS [M+H]⁺ 579.

Example 12(2S)—N-{[N-(1-{[3-(4-Fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopropyl}-2-hydroxy-4-methylpentanamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as an oil. ¹H NMR (300 MHz,CD₃OD) δ 7.00-6.70 (m, 8H), 4.45 (m, 5H), 4.15 (m, 1H), 3.10-3.40 (m,2H), 2.00-1.00 (m, 12H), 0.90, (m, 6H). MS [M+H]⁺ 526.

Example 13(2S)—N-{[N-(1-{[3-(4-Fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopentyl}-2-hydroxy-3-methylbutanamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as an oil. ¹H NMR (300 MHz,CD₃OD) δ 7.20-6.80 (m, 8H), 4.60 (m, 3H), 4.00 (d, 1H), 3.5 (m, 1H),3.20 (m, 1H), 2.40-1.05 (m, 17H), 1.00 (d, 3H), 0.90 (d, 3H). MS [M+H]⁺540.

Example 142,2-Difluoro-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-4-phenylbutanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz, CD₃OD) δ 7.90-7.00 (m,13H), 5.45 (d, 1H), 3.45 (s, 3H), 2.80 (m, 2H), 2.60-2.20 (m, 6H),1.80-1.90 (m, 8H). MS [M+H]⁺ 627.

Example 15N—[(N-{1-Methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-(4-piperidyl)propanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz, CD₃OD) δ 8.00-7.20 (m,9H), 6.10 (s, 1H), 5.40 (d, 1H), 5.15 (s, 2H), 3.60 (m, 1H), 3.40 (s,3H), 3.15 (m, 1H), 2.60-1.20 (m, 14H). MS [M+H]⁺ 584.

Example 16(2S)-2-Hydroxy-4-methyl-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. MS [M+H]⁺ 559.

Example 173-Cyclopropyl-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz, CD₃OD) δ 7.60-7.20 (m,8H), 5.40 (m, 1H), 3.45 (s, 3H), 2.70 (s, 2H), 2.40 (m, 4H), 2.05-1.09(m, 14H), 0.4 (m, 1H), 0.00 (m, 1H). MS [M+H]⁺ 541.

Example 18(Aminocyclopentyl)-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide

The title compound was prepared in a manner similar to that describedfor Example 4. This compound was made from the BZD amine that, as a CBzprotected form, was the first peak of the racemic mixture on theCHIRALCEL AD column with acetonitrile. The product was obtained as anoil. ¹H NMR (300 MHz, CD₃OD) δ 7.20-7.80 (m, 8H), 5.45 (m, 1H), 3.45 (s,3H), 2.20 (m, 3H), 2.00-1.60 (m, 5H). MS [M+H]⁺ 445.

Example 19{[(Aminocyclopentyl)carbonylamino]cyclopentyl}-N-((S)1-methyl-2-oxo-5-phenyl(3H-benzo[f]1,4-diazepin-3-yl))carboxamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as an oil. ¹H NMR (300 MHz,CD₃OD) δ 7.20-7.60 (m, 9H), 5.45 (d, 1H), 3.45 (s, 3H), 2.80-2.00 (m,8H), 1.90-1.50 (m, 8H). MS [M+H]⁺ 445.

Example 20(2R)-2-Hydroxy-3-imidazol-2-yl-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 9.16 (d, 1H), 7.69-7.52(m, 5H), 7.33 (d, 1H), 7.24-7.15 (m, 3H), 5.45 (d, 1H), 3.42 (s, 3H),2.24-2.14 (m, 3H), 2.11-1.84 (m, 1H), 1.83-1.72 (m, 4H), 1.66-1.56 (m,2H); MS [M+H]⁺ 583.

Example 212-Ethoxy-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 8.17 (d, 1H), 7.76-7.60(m, 5H), 7.40 (d, 1H), 7.32-7.23 (m, 1H), 6.99 (s, 1H), 5.52 (d, 1H),4.01 (d, 2H), 3.67-3.60 (q, 2H), 3.48 (s, 3H), 2.48-2.40 (m, 2H),2.14-2.08 (m, 2H), 1.89-1.83 (m, 3H), 1.64 (s, 2H), 1.29 (s, 3H); MS[M+H]⁺ 531.

Example 223-Cyclopentyl-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 8.00 (d, 1H), 7.68-7.51(m, 5H), 7.32 (d, 1H), 7.23-7.17 (m, 2H), 5.85 (s, 1H), 5.41 (d, 1H),3.39 (s, 3H), 2.42-2.22 (m, 2H), 2.20 (t, 2H), 2.10-1.90 (m, 2H),1.76-1.44 (m, 13H), 1.10-1.0 (m, 2H); MS [M+H]⁺ 569.

Example 23(2S)-2-Hydroxy-3-methyl-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]butanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 8.50 (d, 1H), 7.76-7.61(m, 4H), 7.41 (d, 1H), 7.32-7.28 (m, 1H), 7.03 (s, 1H), 5.53-5.51 (m,1H), 4.06 (d, 1H), 3.48 (s, 3H), 2.57-2.35 (m, 2H), 2.30-2.10 (m, 2H),2.09-1.90 (m, 1H), 1.80-1.70 (m, 5H), 1.05 (d, 3H), 0.94 (d, 3H); MS[M+H]⁺ 545.

Example 24(2S)-2-Cyclohexyl-2-hydroxy-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 8.04 (d, 1H), 7.67-7.51(m, 4H), 7.31 (d, 1H), 7.23-7.18 (m, 1H), 7.02 (s, 1H), 5.42 (d, 1H),3.94 (m, 1H), 3.78 (s, 3H), 2.42-2.25 (m, 2H), 2.18-1.90 (m, 2H),1.80-1.65 (m, 9H), 1.30-1.00 (m, 6H); MS [M+H]⁺ 585.

Example 25(2R)-2-Cyclohexyl-2-hydroxy-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]acetamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 8.17 (d, 1H), 7.67-7.52(m, 4H), 7.32 (d, 1H), 7.23-7.15 (m, 1H), 6.89 (s, 1H), 5.45 (d, 1H),3.92 (d, 1H), 3.39 (s, 3H), 2.45-2.25 (m, 2H), 2.10-1.95 (m, 2H),1.80-1.50 (m, 10H), 1.25-1.00 (m, 6H); MS [M+H]⁺ 585.

Example 26(2S)-2-Amino-4-methyl-N—[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 8.95 (s, 1H), 7.79-7.63(m, 5H), 7.40-7.30 (m, 2H), 5.46 (s, 1H), 4.20 (d, 2H), 4.0-3.90 (m,1H), 3.51 (s, 3H), 2.40-2.20 (m, 2H), 2.10 2.00 (m, 2H), 1.90-1.70 (m,4H), 1.40-1.20 (m, 2H), 1.10-1.00 (m, 3H), 1.00-0.90 (m, 3H); MS [M+H]⁺559.

Example 27[(Cyclohexylcarbonylamino)cyclopentyl]-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H-NMR (CDCl₃) 8.10 (d, 1H), 7.75-7.62(m, 3H), 7.42-7.39 (m, 3H), 7.30-7.20 (m, 1H), 6.11 (s, 1H), 5.47 (d,1H), 3.46 (s, 3H), 2.50-2.45 (m, 2H), 2.30-2.10 (m, 1H), 2.09-1.75 (m,9H), 1.70-1.60 (m, 1H), 1.50-1.40 (m, 2H), 1.39-1.20 (m, 3H); MS [M+H]⁺555.

Example 29{[N-(3-Methylbutyl)carbamoyl]cyclopentyl}-N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carboxamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.78-7.60 (m,5H), 7.48-7.22 (m, 3H), 5.47 (d, 1H), 3.49 (s, 3H), 3.30 (m, 2H),2.38-2.22 (m, 4H), 1.84-1.38 (m, 7H), 0.90 (d, 6H). MS [M+H]⁺ 543.

Example 304-Methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.78-7.56 (m,5H), 7.42-7.20 (m, 3H), 5.46 (d, 1H), 3.44 (s, 3H), 2.48-2.20 (m, 4H),2.05 (m, 2H), 1.80 (m, 4H), 1.58 (m, 3H), 0.88 (d, 6H). MS [M+H]⁺ 543.

Example 31(2S)-2-Hydroxy-4-methyl-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.78-7.58 (m,5H), 7.43-7.20 (m, 3H), 5.49 (d, 1H), 4.17 (m, 1H), 3.45 (s, 3H), 2.40(m, 2H), 2.10 (m, 2H), 1.92-1.50 (m, 8H), 0.92 (m, 6H). MS [M+H]⁺ 559.

Example 323-Methoxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]propanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.78-7.56 (m,5H), 7.40-7.20 (m, 3H), 5.51 (d, 1H), 3.72 (m, 2H), 3.44 (s, 3H), 3.39(s, 3H), 2.58-2.30 (m, 4H), 2.02 (m, 2H), 1.88 (m, 4H). MS [M+H]⁺ 531.

Example 33(2S)-2-Hydroxy-N-[(N-{1-methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-3-phenylpropanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.72-7.57 (m,5H), 7.40-7.20 (m, 3H), 5.48 (d, 1H), 4.37 (m, 1H), 3.42 (s, 3H), 3.20(q, 1H), 2.97 (q, 1H), 2.38 (m, 2H), 1.96 (m, 2H), 1.80-1.52 (m, 4H). MS[M+H]⁺ 593.

Example 34N-[(N-{1-Methyl-2-oxo-5-[4-(trifluoromethyl)phenyl](3H-benzo[f]1,4-diazepin-3-yl)}carbamoyl)cyclopentyl]-2-(phenylmethoxy)acetamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino benzodiazepine employed in Example 1. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.74-7.55 (m,5H), 7.40-7.20 (m, 3H), 5.48 (d, 1H), 4.61 (q, 2H), 4.12 (q, 2H), 3.44(s, 3H), 2.42 (m, 2H), 2.05 (m, 2H), 1.80 (m, 4H). MS [M+H]⁺ 593.

Example 35(2S)-2-Hydroxy-3-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-butanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino bisbenzazepine employed in Example 10. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.64-7.35 (m,8H), 5.25 (d, 1H), 4.06 (d, 1H), 3.35 (s, 3H), 2.42-2.05 (m, 6H), 1.80(m, 4H), 1.05 (d, 3H), 0.95 (d, 3H). MS [M+H]⁺ 450.

Example 36(2S)-2-Hydroxy-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino bisbenzazepine employed in Example 10. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.64-7.32 (m,8H), 5.24 (d, 1H), 4.20 (q, 1H), 3.34 (s, 3H), 2.38 (m, 2H), 2.20-1.60(m, 9H), 0.97 (m, 6H). MS [M+H]⁺ 464.

Example 373-Cyclopentyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}propanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino bisbenzazepine employed in Example 10. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.64-7.35 (m,8H), 5.25 (d, 1H), 3.36 (s, 3H), 2.42-1.45 (m, 21H). MS [M+H]⁺ 474.

Example 38(2S)-2-Cyclohexyl-2-hydroxy-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-acetamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino bisbenzazepine employed in Example 10. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.62-7.36 (m,8H), 5.24 (d, 1H), 3.98 (d, 1H), 3.33 (s, 3H), 2.42-1.04 (m, 19H). MS[M+H]⁺ 490.

Example 393-Cyclopropyl-N-{[N-((S)-5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-propanamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as an oil. ¹H NMR (300 MHzCDCl₃) 7.56-7.24 (m, 8H), 5.16 (d, 1H), 3.27 (s, 3H), 2.38-2.15 (m, 4H),2.10-1.82 (m, 2H), 1.78-1.42 (m, 6H), 0.64 (m, 1H), 0.36 (m, 2H), 0.02(m, 2H). MS [M+H]⁺ 446.

Example 40N-{[N-(1-Butyl-5-cyclopentyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide

The amino benzodiazepine core was made in a manner similar to thatdescribed in the Scheme 6. The title compound was prepared in a mannersimilar to that described for Example 4. The product was obtained as anoil. ¹H NMR (300 MHz CDCl₃) 7.60-7.22 (m, 4H), 5.25 (d, 1H), 4.36 (m,1H), 3.56 (m, 1H), 3.31 (m, 1H), 2.40-0.78 (m, 34H). MS [M+H]⁺ 509.

Example 41N-{[N-(5-Cyclopentyl-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl))carbamoyl]cyclopentyl}-4-methylpentanamide

The amino benzodiazepine core was made in a manner similar to thatdescribed in the Scheme 6. The title compound was prepared in a mannersimilar to that described for Example 4. The product was obtained as anoil. ¹H NMR (300 MHz CDCl₃) 7.58-7.20 (m, 4H), 5.30 (d, 1H), 3.38 (s,3H), 3.30 (m, 1H), 2.40-1.20 (m, 21H), 0.89 (d, 6H). MS [M+H]⁺ 467.

Example 42(2S)-2-Hydroxy-3-methyl-N-({N-[2-oxo-1-benzyl(3H,4H,5H-benzo[f]azaperhydroepin-3-yl)]carbamoyl}cyclopentyl)butanamide

The amino benzoazepine core was made in a manner similar to thatdescribed in J. Med. Chem. 1999, 42, 2621. The title compound wasprepared in a manner similar to that described for Example 4. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.34-7.10 (m,9H), 5.16 (m, 1H), 4.76 (m, 1H), 4.42 (m, 1H), 3.94 (m, 1H), 2.64-1.64(m, 13H), 1.00-0.86 (m, 6H). MS [M+H]⁺ 478.

Example 43(2S)-4-Methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-2-[(propylsulfonyl)amino]pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino bisbenzazepine employed in Example 10. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.62-7.32 (m,8H), 5.40 (d, 1H), 5.24 (d, 1H), 4.02 (m, 1H), 3.34 (s, 3H), 2.98 (m,2H), 2.42-1.58 (m, 13H), 0.94-0.85 (m, 9H). MS [M+H]⁺ 569.

Example 44(2S)-2-Amino-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino bisbenzazepine employed in Example 10. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.60-7.30 (m,8H), 5.22 (d, 1H), 3.32 (s, 3H), 3.08 (m, 1H), 2.48 (s, 3H), 2.46-1.45(m, 11H), 0.98-0.92 (q, 6H). MS [M+H]⁺ 477.

Example 452,2-Difluoro-4-methyl-N-{[N-(5-methyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4 using the amino bisbenzazepine employed in Example 10. Theproduct was obtained as an oil. ¹H NMR (300 MHz CDCl₃) 7.62-7.30 (m,8H), 5.23 (d, 1H), 3.34 (s, 3H), 2.42-1.80 (m, 11H), 1.00 (d, 6H). MS[M+H]⁺ 484.

Example 564-Methyl-N-{[N-(6-oxo(5H,7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide

The title compound was prepared in a manner similar to that describedfor Example 4. The product was obtained as an oil. ¹H NMR (300 MHz,CD₃OD): δ 7.91 (d, J=6.7 Hz, 1H), 7.63 (m, 1H), 7.51-7.28 (m, 7H), 7.08(d, J=7.0 Hz, 1H), 5.84 (s, 1H), 5.25 (d, J=6.7 Hz, 1H), 2.41-0.89 (m,19H); ESI MS m/z=434 [C₂₆H₃₁N₃O₃+H]⁺.

Example 57N-({N-[5-(3,3-Dimethyl-2-oxobutyl)-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

To a solution of4-methyl-N-{[N-(6-oxo(5H,7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}pentanamide(540 mg, 1.3 mmol), in DMF (25 mL) was added K₂CO₃ (0.52 g, 3.7 mmol)and bromopinacolone (0.45 g, 2.5 mmol), and the solution was allowed tostir for 40 h at room temperature. The contents of the flask werepartitioned between EtOAc and a 5% LiCl solution (150 mL each), theorganic phase washed with 5% LiCl (2×50 mL), dried over anhydrous Na₂SO₄and concentrated to yield a white solid. This was further purified bycolumn chromatography [silica gel, EtOAc/hexanes (35:65)] to yield thetitle compound (340 mg, 51%) as a white solid. The title compound wereseparated by chiral HPLC using the following conditions: Column,Chiralpak AD column (5 cm×50 cm); Eluent, 96:4 Hexanes/2-Propanol; Flowrate, 100 mL/min; Monitoring wavelength, 220 nm.

-   -   Enantiomer A: 158 mg: mp 126-130° C.; ¹H NMR (300 MHz, CDCl₃) δ        7.89 (d, J=6.7 Hz, 1H), 7.62-7.13 (m, 8H), 5.82 (s, 1H), 5.35        (d, J=7.4 Hz, 1H), 4.62 (q_(ab), J=14.1 Hz, 2H), 2.47-1.59 (m,        13H), 1.22 (s, 9H), 0.92 (d, J=5.8 Hz, 6H); IR (KBr) 3410, 2958,        2475, 1724, 1663 cm⁻¹; ESI MS m/z=532 [C₃₂H₄₁N₃O₄+H]⁺; HPLC        97.8%, t_(r)=24.83 min. (HPLC Conditions A).    -   Enantiomer B: 165 mg; mp 126-130° C.; ¹H NMR (300 MHz, CDCl₃) δ        7.89 (d, J=6.7 Hz, 1H), 7.62-7.13 (m, 8H), 5.82 (s, 1H), 5.35        (d, J=7.4 Hz, 1H), 4.62 (q_(ab), J=14.1 Hz, 2H), 2.47-1.59 (m,        13H), 1.22 (s, 9H), 0.92 (d, J=5.8 Hz, 6H); IR (KBr) 3410, 2958,        2475, 1724, 1663 cm⁻¹; ESI MS m/z=532 [C₃₂H₄₁N₃O₄ ⁺H]⁺; HPLC        97.8%, t_(r)=24.83 min. (HPLC Conditions A).

Example 584-Methyl-N-[(N-{6-oxo-5-[(3-phenoxyphenyl)methyl](7H-dibenzo[d,f]azaperhydroepin-7-yl)}carbamoyl)cyclopentyl]pentanamide

The title compound was prepared in a manner similar to that describedfor Example 57. The product was obtained as a white solid: mp 94-100°C.; ¹H NMR (500 MHz, CDCl₃) δ 7.99 (d, J=6.9 Hz, 1H), 7.58-6.43 (m,17H), 5.82 (s, 1H), 5.39 (d, J=7.4 Hz, 1H), 5.12 (q_(ab), J=14.5 Hz,2H), 2.47-1.57 (m, 13H), 0.82 (d, J=6.1 Hz, 6H); IR (KBr) 3332, 2955,1660, 1584, 1487 cm⁻¹; ESI MS m/z=616 [C₃₉H₄₁N₃O₄+H]⁺; HPLC 99.4%,t_(r)=19.54 min. (HPLC Conditions A).

Example 59N-{[N-(5-Butyl-6-oxo(7H-dibenzo[d,f]azaperhydroepin-7-yl))carbamoyl]cyclopentyl}-4-methylpentanamide

The title compound was prepared in a manner similar to that describedfor Example 57. The product was obtained as a white solid. Theenantiomers were separated by chiral HPLC using the followingconditions: Column, Chiralcel OD column (5 cm×50 cm); Eluent, 95:5Hexanes/2-Propanol; Flow rate, 100 mL/min; Monitoring wavelength, 270nm.

-   -   Enantiomer A: 197 mg: mp 123-126° C.; ¹H NMR (500 MHz, CDCl₃) δ        7.99 (d, J=7.0 Hz, 1H), 7.58-6.43 (m, 8H), 5.91 (s, 1H), 5.26        (d, J=7.4 Hz, 1H), 4.29 (m, 2H), 3.52 (m, 2H), 2.43-1.19 (m,        15H), 0.95 (d, J=6.1 Hz, 6H), 0.62 (m, 3H); IR (KBr) 3325, 2957,        2871, 1655, 1498 cm⁻¹; ESI MS m/z=490 [C₃₀H₃₉N₃O₃+H]⁺; HPLC        100%, t_(r)=20.25 min. (HPLC Conditions A).    -   Enantiomer B: 167 mg: mp 110-115° C.; ¹H NMR (500 MHz, CDCl₃) δ        7.99 (d, J=7.0 Hz, 1H), 7.58-6.43 (m, 8H), 5.91 (s, 1H), 5.26        (d, J=7.4 Hz, 1H), 4.29 (m, 2H), 3.52 (m, 2H), 2.43-1.19 (m,        15H), 0.95 (d, J=6.1 Hz, 6H), 0.62 (m, 3H); IR (KBr) 3325, 2957,        2871, 1655, 1498 cm⁻¹; ESI MS m/z=490 [C₃₀H₃₉N₃O₃+H]⁺; HPLC        100%, t_(r)=20.26 min. (HPLC Conditions A).

Example 604-Methyl-N-({N-[6-oxo-5-benzyl(7H-dibenzo[d,f]azaperhydroepin-7-yl)]carbamoyl}cyclopentyl)pentanamide

The title compound was prepared in a manner similar to that describedfor Example 57. The product was obtained as a white solid: mp 103-106°C.; ¹H NMR (500 MHz, CDCl₃) δ 8.01 (d, J=6.8 Hz, 1H), 7.52-7.25 (m, 8H),7.05 (m, 3H), 6.78 (m, 2H), 5.84 (s, 1H), 5.36 (d, J=7.4 Hz, 1H), 5.04(q_(ab), J=14.7 Hz, 2H), 2.41-1.26 (m, 13H), 0.91 (d, J=5.8 Hz, 6H); IR(KBr) 3325, 2956, 1655, 1498, 1396 cm⁻¹; ESI MS m/z=524 [C₃₃H₃₇N₃O₃+H]⁺;HPLC 100%, t_(r)=27.04 min. (HPLC Conditions A).

Example 61N-({N-[5-(tert-Butyl)-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

c) Preparation of 25

To a stirred solution of 23 (see Scheme 6) (1.0 equiv) in CH₂Cl₂ (0.1 M)was added a 30% solution of HBr in acetic acid (16 equiv). The mixturewas stirred for 14 h. The reaction mixture was concentrated in vacuo anddissolved in EtOAc and water and separated. The aqueous layer was madebasic using 6 N NaOH and was extracted with CH₂Cl₂. The organic extractswere washed with brine, dried over Na₂SO₄, filtered and concentrated.The resulting solid was dissolved in CH₂Cl₂ and added to a stirringsolution of the acid 24 (1.2 equiv), EDC-HCl (1.5 equiv), HOBt (1.5equiv), and DIPEA (5.0 equiv) in CH₂Cl₂ (0.15 M). The reaction wasstirred overnight, quenched with water, washed with 20% citric acid(3×), sat NaHCO₃ (2×), brine, dried over Na₂SO₄, filtered andconcentrated. Crude material was recrystallized from EtOAc and Et₂O togive 25 (4.4 g, 95%) as a white powder: ¹H NMR (500 MHz, CDCl₃) δ7.71-6.98 (m, 6H), 5.87 (s, 1H), 5.29 (d, 1H), 2.38 (m, 2H), 2.21 (t,2H) 2.01 (m, 2H), 1.52 (m, 7H), 1.23 (s, 9H), 0.88 (d, 6H).

d) Preparation of Example 61.

To a suspension of 25 (1 equiv) and freshly powdered K₂CO₃ (3.0 equiv)in DMF (0.05 M) was added methyl iodide (1.5 equiv). The mixture wasstirred (5 h). To the reaction was added EtOAc and water and the layersseparated. The organic layer was washed with 5% LiCl (2×), brine, driedover Na₂SO₄, filtered and concentrated. The resulting material wasdissolved in Et₂O and concentrated in vacuo providingN-({N-[5-(tert-butyl)-1-methyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}-cyclopentyl)-4-methylpentanamide(60 mg, 66%) as a white powder: mp 175-178° C.; ¹H NMR (500 MHz, CDCl₃)δ 7.71-7.17 (m, 5H), 5.89 (s, 1H), 5.23 (d, 1H), 3.34 (s, 3H), 2.41-2.29(m, 3H), 2.21 (m, 2H), 2.04 (m, 3H), 1.80 (m, 4H), 1.60 (m, 1H), 1.18(s, 9H), 0.90 (d, 6H); ESI MS m/z=455 [C₂₆H₃₈N₄O₃+H]⁺; IR (KBr)=3324,2958, 1677, 1508, 1366, 1197 cm⁻¹; HPLC 96.8%, t_(r)=15.75 min. (HPLCConditions A).

Example 62N-({N-[5-(tert-Butyl)-1-butyl-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

The title compound was prepared in a manner similar to that describedfor Example 62. The product was obtained as a white powder (450 mg,70%): mp 175-177° C.; ¹H NMR (500 MHz, CDCl₃) δ 7.71-7.13 (m, 5H), 5.89(s, 1H), 5.20 (d, 1H), 4.36 (m, 1H), 3.50 (m, 1H), 2.32 (m, 3H) 2.20 (m,2H), 2.02 (m, 3H), 1.80 (m, 4H), 1.57 (m, 1H), 1.35 (m, 2H) 1.26 (s,9H), 1.21 (m, 2H), 0.89 (d, 6H), 0.83 (t, 3H); ESI MS m/z=497[C₂₉H₄₄N₄O₃+H]⁺; IR (KBr)=3321, 2959, 2363, 1676, 1508, 1365 cm⁻¹; HPLC95.4%, t_(r)=19.69 min. (HPLC Conditions A).

Example 63N-({N-[5-Butyl-2-oxo-1-(2-pyridylmethyl)(3H-benzo[f]1,4-diazepin-3-yl)]carbamoyl}cyclopentyl)-4-methylpentanamide

The title compound was prepared in a manner similar to that describedfor Example 62. The product was obtained as a white powder: mp 63-67°C.; ¹H NMR (CDCl₃) δ 8.46-7.11 (m, 8H), 5.89 (s, 1H), 5.40 (d, J=6.87Hz, 1H), 5.28 (d, J=15.77 Hz, 1H), 5.12 (d, J=15.82 Hz, 1H), 2.74 (m,2H), 2.43-0.77 (m, 27H); ESI MS m/z=532 [C₃₁H₄₁N₅O₃+H]⁺; IR (KBr) 3310(br.), 1670 cm⁻¹; HPLC >95% t_(r)=17.07 min. (HPLC Conditions A). Anal.Calcd for [C₃₁H₄₁N₅O₃.0.5H₂O]: C, 68.86; H, 7.83; N, 12.95. Found: C,68.73; H, 7.86; N, 12.79.

Tables 1-4 below provide representative Examples of the compounds ofFormula (I) of the present invention.

TABLE 1

Ex # R³ L C —WXYZ R¹¹  2 3-Me-butyl NHC(═O) cyclopentyl Me phenyl  3n-butyl NHC(═O) cyclopentyl Me phenyl  4 3,5-diF- C(═O)NH cyclohexyl Mephenyl benzyl  5 3,5-diF- C(═O)NH cyclopentyl Me phenyl benzyl  63,5-diF- C(═O)NH cyclopropyl Me phenyl benzyl  7 cyclopentyl C(═O)NHcyclohexyl Me phenyl ethyl  8 3,5-diF- C(═O)NH 4-piperidyl Me phenylbenzyl  9 3,5-diF- C(═O)NH N- Me phenyl benzyl benzloxy- carbonyl-4-piperidyl 11 benzyl O—C(═O)NH cyclopentyl Me 4-CF₃- phenyl 143-phenyl-1, C(═O)NH cyclopentyl Me 4-CF₃- 1-diF-propyl phenyl 15 2-(4-C(═O)NH cyclopentyl Me 4-CF₃- piperidyl) phenyl ethyl 16 1-hydroxy-3-C(═O)NH cyclopentyl Me 4-CF₃- Me-butyl phenyl 17 2-cyclo- C(═O)NHcyclopentyl Me 4-CF₃- propyl- phenyl ethyl 19 1-amino C(═O)NHcyclopentyl Me phenyl cyclopentyl 20 1-hydroxy-2- C(═O)NH cyclopentyl Me4-CF₃- imidazol-2- phenyl yl-ethyl 21 ethyoxy- C(═O)NH cyclopentyl Me4-CF₃- methyl phenyl 22 2-cyclopentyl- C(═O)NH cyclopentyl Me 4-CF₃-cyclopentyl- phenyl ethyl 23 1-hydroxy- C(═O)NH cyclopentyl Me 4-CF₃-2-Me- phenyl propyl 24* 1-hydroxy-1- C(═O)NH cyclopentyl Me 4-CF₃-cyclohexyl- phenyl methyl 25* 1-hydroxy-1- C(═O)NH cyclopentyl Me 4-CF₃-cyclohexyl- phenyl methyl 26 1-NH₂- C(═O)NH cyclopentyl Me 4-CF₃-3-Me-butyl phenyl 27 cyclohexyl C(═O)NH cyclopentyl Me 4-CF₃- phenyl 293-Me-butyl NHC(═O) cyclopentyl Me 4-CF₃- phenyl 30 3-Me-butyl C(═O)NHcyclopentyl Me 4-CF₃- phenyl 31 1-hydroxy-3- C(═O)NH cyclopentyl Me4-CF₃- Me-butyl phenyl 32 2-methoxy- C(═O)NH cyclopentyl Me 4-CF₃- ethylphenyl 33 1-hydroxy-2- C(═O)NH cyclopentyl Me 4-CF₃- phenyl-ethyl phenyl34 benzyloxy- C(═O)NH cyclopentyl Me 4-CF₃- methyl phenyl 39 2-cyclo-C(═O)NH cyclopentyl Me phenyl propyl- ethyl 40 3-Me-butyl C(═O)NHcyclopentyl n-butyl cyclo- pentyl 41 3-Me-butyl C(═O)NH cyclopentyl Mecyclo- pentyl 61 3-Me-butyl C(═O)NH cyclopentyl Me t-butyl 62 3-Me-butylC(═O)NH cyclopentyl n-butyl t-butyl 63 3-Me-butyl C(═O)NH cyclopentyl 2-n-butyl pyridyl- methyl *stereoisomers

TABLE 2

Ex. # R³ L C Z-Y—X—W—  1 3-Me-butyl NHC(═O) cyclopentyl Me 10 3-Me-butylC(═O)NH cyclopentyl Me 35 1-hydroxy-2-Me- C(═O)NH cyclopentyl Me propyl36 1-hydroxy-3-Me- C(═O)NH cyclopentyl Me butyl 37 2-cyclopentyl-ethylC(═O)NH cyclopentyl Me 38 1-hydroxy-1- C(═O)NH cyclopentyl Mecyclohexyl-methyl 43 1-(propyl- C(═O)NH cyclopentyl Me sulfamide)-3-Me-butyl 44 1-(N-Me-amino)-3- C(═O)NH cyclopentyl Me Me-butyl 451,1-diF-3-Me-butyl C(═O)NH cyclopentyl Me 56 3-Me-butyl C(═O)NHcyclopentyl H 57 3-Me-butyl C(═O)NH cyclopentyl 3,3-dimethyl-2- oxobutyl58 3-Me-butyl C(═O)NH cyclopentyl 3-phenoxy- benzyl 59 3-Me-butylC(═O)NH cyclopentyl n-butyl 60 3-Me-butyl C(═O)NH cyclopentyl benzyl

TABLE 3

Ex. # R³ L C Z-Y—X—W— 12 1-hydroxy-3-Me- C(═O)NH cyclopropyl3-(4-F-phenoxy)- butyl benzyl 13 1-hydroxy-3-Me- C(═O)NH cyclopentyl3-(4-F-phenoxy)- propyl benzyl

TABLE 4

Ex. # R³ L C Z-Y—X—W— 42 1-hydroxy-2-Me- C(═O)NH cyclopentyl benzylpropyl

Utility

Aβ production has been implicated in the pathology of Alzheimer'sDisease (AD). The compounds of the present invention have utility forthe prevention and treatment of AD by inhibiting Aβ production. Methodsof treatment target formation of Aβ production through the enzymesinvolved in the proteolytic processing of β amyloid precursor protein.Compounds that inhibit β or γ secretase activity, either directly orindirectly, control the production of Aβ. Such inhibition of β or γsecretases reduces production of Aβ, and is expected to reduce orprevent the neurological disorders associated with Aβ protein, such asAlzheimer's Disease.

Cellular screening methods for inhibitors of Aβ production, testingmethods for the in vivo suppression of Aβ production, and assays for thedetection of secretase activity are known in the art and have beendisclosed in numerous publications, including J. Med. Chem. 1999, 42,3889-3898, PCT publication number WO 98/22493, EPO publication number0652009, U.S. Pat. No. 5,703,129 and U.S. Pat. No. 5,593,846; all herebyincorporated by reference.

The compounds of the present invention have utility for the preventionand treatment of disorders involving Aβ production, such ascerebrovascular disorders.

Compounds of Formula (I) are expected to possess γ-secretase inhibitoryactivity. The γ-secretase inhibitory activity of the compound of thepresent invention is demonstrated using assays for such activity, forexample, using the assay described below. Compounds of the presentinvention have been shown to inhibit the activity of γ-secretase, asdetermined by the Aβ immunoprecipitation assay.

Compounds provided by this invention should also be useful as a standardand reagent in determining the ability of a potential pharmaceutical toinhibit Aβ production. These would be provided in commercial kitscomprising a compound of this invention.

As used herein “μg” denotes microgram, “mg” denotes milligram, “g”denotes gram, “μL” denotes microliter, “mL” denotes milliliter, “L”denotes liter, “nM” denotes nanomolar, “μM” denotes micromolar, “mM”denotes millimolar, “M” denotes molar, “nm” denotes nanometer, “SDS”denotes sodium dodecyl sulfate, and “DMSO” denotes dimethyl sulfoxide,and “EDTA” denotes ethylenediaminetetraacetic acid.

A compound is considered to be active if it has an IC₅₀ or K_(i) valueof less than about 100 μM for the inhibition of Aβ production.Preferrably the IC₅₀ or K_(i) value is less than about 10 μM; morepreferrably the IC₅₀ or K_(i) value is less than about 0.1 μM. Thepresent invention has been shown to inhibit Aβ protein production withan IC₅₀ or K_(i) value of less than 100 μM.

β Amyloid Precursor Protein Accumulation Assay

A novel assay to evaluate the accumulation of Aβ protein was developedto detect potential inhibitors of secretase. The assay uses the N 9 cellline, characterized for expression of exogenous APP by immunoblottingand immunoprecipitation.

The effect of test compounds on the accumulation of Aβ in theconditioned medium is tested by immunoprecipitation. Briefly, N 9 cellsare grown to confluency in 6-well plates and washed twice with 1× Hank'sbuffered salt solution. The cells are starved in methionine/cysteinedeficient media for 30 min, followed by replacement with fresh deficientmedia containing 150 uCi S35 Translabel (Amersham). Test compoundsdissolved in DMSO (final concentration 1%) are added together with theaddition of radiolabel. The cells are incubated for 4 h at 37° C. in atissue culture incubator.

At the end of the incubation period, the conditioned medium is harvestedand pre-cleared by the addition of 5 μl normal mouse serum and 50 μl ofprotein A Sepharose (Pharmacia), mixed by end-over-end rotation for 30minutes at 4° C., followed by a brief centrifugation in a microfuge. Thesupernatant is then harvested and transferred to fresh tubes containing5 ug of a monoclonal antibody (clone 1101.1; directed against aninternal peptide sequence in Aβ) and 50 μl protein A Sepharose. Afterincubation overnight at 4° C., the samples are washed three times withhigh salt washing buffer (50 mM Tris, pH 7.5, 500 mM NaCl, 5 mM EDTA,0.5% Nonidet P-40), three times with low salt wash buffer (50 mM Tris,pH 7.5, 150 mM NaCl, 5 mM EDTA, 0.5% Nonidet P-40), and three times with10 mM Tris, pH 7.5. The pellet after the last wash is resuspended in SDSsample buffer (Laemmli, 1970) and boiled for 3 minutes. The supernatantis then fractionated on either 10-20% Tris/Tricine SDS gels or on 16.5%Tris/Tricine SDS gels. The gels are dried and exposed to X-ray film oranalyzed by phosphorimaging. The resulting image is analyzed for thepresence of Aβ polypeptides. The steady-state level of Aβ in thepresence of a test compound is compared to wells treated with DMSO (1%)alone. A typical test compound blocks Aβ accumulation in the conditionedmedium, and is therefore considered active, with an IC₅₀ less than 100μM.

C-Terminus β Amyloid Precursor Protein Accumulation Assay

The effect of a test compound on the accumulation of C-terminalfragments is determined by immunoprecipitation of APP and fragmentsthereof from cell lysates. N 9 cells are metabolically labeled as abovein the presence or absence of test compounds. At the end of theincubation period, the conditioned medium are harvested and cells lysedin RIPA buffer (10 mM Tris, pH 8.0 containing 1% Triton X-100, 1%deoxycholate, 0.1% SDS, 150 mM NaCl, 0.125% NaN₃). Again, lysates areprecleared with 5 ul normal rabbit serum/50 ul protein A Sepharose,followed by the addition of BC-1 antiserum (15 μl;) and 50 μl protein ASepharose for 16 hours at 4° C. The immunoprecipitates are washed asabove, bound proteins eluted by boiling in SDS sample buffer andfractionated by Tris/Tricine SDS-PAGE. After exposure to X-ray film orphosphorimager, the resulting images are analyzed for the presence ofC-terminal APP fragments. The steady-state level of C-terminal APPfragments is compared to wells treated with DMSO (1%) alone. A typicaltest compound stimulates C-terminal fragment accumulation in the celllysates, and is therefore considered active, with an IC₅₀ less than 100μM.

Aβ-Immunoprecipitation Assay

This immunoprecipitation assay is specific for γ-secretase (i.e.,proteolytic activity required to generate the C-terminal end of Aβeither by direct cleavage or generating a C-terminal extended specieswhich is subsequently further proteolyzed). N 9 cells are pulse labeledin the presence of a reported γ-secretase inhibitor (MDL 28170) for 1 h,followed by washing to remove radiolabel and MDL 28170. The media isreplaced and test compounds are added. The cells are chased forincreasing periods of times and Aβ is isolated from the conditionedmedium and C-terminal fragments from cell lysates (see above). The testcompound is characterized whether a stabilization of C-terminalfragments is observed and whether Aβ is generated from these accumulatedprecursor. A typical test compound prevents the generation of Aβ out ofaccumulated C-terminal fragments and is considered active with an IC₅₀less than 100 μM.

Dosage and Formulation

The compound of the present invention can be administered orally usingany pharmaceutically acceptable dosage form known in the art for suchadministration. The active ingredient can be supplied in solid dosageforms such as dry powders, granules, tablets or capsules, or in liquiddosage forms, such as syrups or aqueous suspensions. The activeingredient can be administered alone, but is generally administered witha pharmaceutical carrier. A valuable treatise with respect topharmaceutical dosage forms is Remington's Pharmaceutical Sciences, MackPublishing.

The compound of the present invention can be administered in such oraldosage forms as tablets, capsules (each of which includes sustainedrelease or timed release formulations), pills, powders, granules,elixirs, tinctures, suspensions, syrups, and emulsions. Likewise, theymay also be administered in intravenous (bolus or infusion),intraperitoneal, subcutaneous, or intramuscular form, all using dosageforms well known to those of ordinary skill in the pharmaceutical arts.An effective but non-toxic amount of the compound desired can beemployed to prevent or treat neurological disorders related to β-amyloidproduction or accumulation, such as Alzheimer's disease and Down'sSyndrome.

The compound of this invention can be administered by any means thatproduces contact of the active agent with the agent's site of action inthe body of a host, such as a human or a mammal. The compound can beadministered by any conventional means available for use in conjunctionwith pharmaceuticals, either as individual therapeutic agents or in acombination of therapeutic agents. The compound can be administeredalone, but generally administered with a pharmaceutical carrier selectedon the basis of the chosen route of administration and standardpharmaceutical practice.

The dosage regimen for the compound of the present invention will, ofcourse, vary depending upon known factors, such as the pharmacodynamiccharacteristics of the particular agent and its mode and route ofadministration; the species, age, sex, health, medical condition, andweight of the recipient; the nature and extent of the symptoms; the kindof concurrent treatment; the frequency of treatment; the route ofadministration, the renal and hepatic function of the patient, and theeffect desired. An ordinarily skilled physician or veterinarian canreadily determine and prescribe the effective amount of the drugrequired to prevent, counter, or arrest the progress of the condition.

Advantageously, the compounds of the present invention may beadministered in a single daily dose, or the total daily dosage may beadministered in divided doses of two, three, or four times daily.

The compound for the present invention can be administered in intranasalform via topical use of suitable intranasal vehicles, or via transdermalroutes, using those forms of transdermal skin patches wall known tothose of ordinary skill in that art. To be administered in the form of atransdermal delivery system, the dosage administration will, of course,be continuous rather than intermittent throughout the dosage regimen.

In the methods of the present invention, the compound herein describedin detail can form the active ingredient, and is typically administeredin admixture with suitable pharmaceutical diluents, excipients, orcarriers (collectively referred to herein as carrier materials) suitablyselected with respect to the intended form of administration, that is,oral tablets, capsules, elixirs, syrups and the like, and consistentwith conventional pharmaceutical practices.

For instance, for oral administration in the form of a tablet orcapsule, the active drug component can be combined with an oral,non-toxic, pharmaceutically acceptable, inert carrier such as lactose,starch, sucrose, glucose, methyl cellulose, magnesium stearate,dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like;for oral administration in liquid form, the oral drug components can becombined with any oral, non-toxic, pharmaceutically acceptable inertcarrier such as ethanol, glycerol, water, and the like. Moreover, whendesired or necessary, suitable binders, lubricants, disintegratingagents, and coloring agents can also be incorporated into the mixture.Suitable binders include starch, gelatin, natural sugars such as glucoseor β-lactose, corn sweeteners, natural and synthetic gums such asacacia, tragacanth, or sodium alginate, carboxymethylcellulose,polyethylene glycol, waxes, and the like. Lubricants used in thesedosage forms include sodium oleate, sodium stearate, magnesium stearate,sodium benzoate, sodium acetate, sodium chloride, and the like.Disintegrators include, without limitation, starch, methyl cellulose,agar, bentonite, xanthan gum, and the like.

The compound of the present invention can also be administered in theform of liposome delivery systems, such as small unilamellar vesicles,large unilamallar vesicles, and multilamellar vesicles. Liposomes can beformed from a variety of phospholipids, such as cholesterol,stearylamine, or phosphatidylcholines.

Compound of the present invention may also be coupled with solublepolymers as targetable drug carriers. Such polymers can includepolyvinylpyrrolidone, pyran copolymer,polyhydroxypropylmethacrylamide-phenol,polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysinesubstituted with palmitoyl residues. Furthermore, the compounds of thepresent invention may be coupled to a class of biodegradable polymersuseful in achieving controlled release of a drug, for example,polylactic acid, polyglycolic acid, copolymers of polylactic andpolyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid,polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, andcrosslinked or amphipathic block copolymers of hydrogels.

Gelatin capsules may contain the active ingredient and powderedcarriers, such as lactose, starch, cellulose derivatives, magnesiumstearate, stearic acid, and the like. Similar diluents can be used tomake compressed tablets. Both tablets and capsules can be manufacturedas sustained release products to provide for continuous release ofmedication over a period of hours. Compressed tablets can be sugarcoated or film coated to mask any unpleasant taste and protect thetablet from the atmosphere, or enteric coated for selectivedisintegration in the gastrointestinal tract.

Liquid dosage forms for oral administration can contain coloring andflavoring to increase patient acceptance. In general, water, a suitableoil, saline, aqueous dextrose (glucose), and related sugar solutions andglycols such as propylene glycol or polyethylene glycols are suitablecarriers for parenteral solutions. Solutions for parenteraladministration preferably contain a water soluble salt of the activeingredient, suitable stabilizing agents, and if necessary, buffersubstances. Antioxidizing agents such as sodium bisulfite, sodiumsulfite, or ascorbic acid, either alone or combined, are suitablestabilizing agents. Also used are citric acid and its salts and sodiumEDTA. In addition, parenteral solutions can contain preservatives, suchas benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

Suitable pharmaceutical carriers are described in Remington'sPharmaceutical Sciences, Mack Publishing Company, a standard referencetext in this field.

1. A process for preparing a compound of Formula (I),

or a stereoisomer, or a pharmaceutically acceptable salt thereof,comprising an amide bond synthesis coupling a carboxylic acid 1 and anamine 2 including amide coupling methods comprising HATU, TBTU, BOP,EDC, CDI, and DCC-mediated couplings:

wherein the product, 3, comprises Formula (I) wherein: L is —NR²⁶C(═O)—,—C(═O)NR²⁶—, —NR²⁶C(═O)O—, —OC(═O)NR²⁶, or —NR²⁶C(═O)NR²⁶—; R³ is—(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(l)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—O—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—S(═O)₂—(CR⁷R^(7a))_(m)—-R⁴,—(CR⁷R^(7a))_(l)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—C(═O)N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))S(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(l)—S(═O)₂N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴; n is 0, 1, 2, or 3;m is 0, 1, 2, or 3; l is 1, 2, or 3; Ring C is a 3 to 8 memberedcarbocycle, wherein the carbocycle is saturated or partially saturated;optionally, the carbocycle contains a heteroatom selected from —O—, —S—,—S(═O)—, —S(═O)₂—, and —N(R²⁰)—; and wherein the carbocycle issubstituted with 0-4 R²¹; R⁴ is H, OH, OR^(14a), C₁-C₈ alkyl substitutedwith 0-3 R^(4a), C₂-C₈ alkenyl substituted with 0-3 R^(4a), C₂-C₈alkynyl substituted with 0-3 R^(4a), C₃-C₁₀ carbocycle substituted with0-3 R^(4b), aryl substituted with 0-3 R^(4b), or 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀carbocycle substituted with 0-3 R^(4b), aryl substituted with 0-3R^(4b), and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R⁶ isH; C₁-C₆ alkyl substituted with 0-3 R^(6a); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(6b); or aryl substituted with 0-3 R^(6b);R^(6a), at each occurrence, is independently selected from H, C₁-C₆alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃; R^(6b),at each occurrence, is independently selected from H, OH, Cl, F, Br, I,CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, andC₁-C₄ haloalkoxy; R⁷, at each occurrence, is independently selected fromH, OH, Cl, F, Br, I, CN, NO₂, CF₃, C₁-C₄ alkyl, phenyl substituted with0-5 R^(7c); R^(7a), at each occurrence, is independently selected fromH, Cl, F, Br, I, CN, CF₃, and C₁-C₄ alkyl; R^(7b) is independentlyselected from H and C₁-C₄ alkyl; R^(7c), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, CF₃, C₁-C₄ alkoxy,and C₁-C₄ alkyl; B is

R¹¹ is H, C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷,C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionallysubstituted with 0-3 R^(11a); aryl substituted with 0-3 R^(11b); C₃-C₁₀carbocycle substituted with 0-3 R^(11b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(11b); R^(11a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; W is —(CR⁸R^(8a))_(p)—; pis 0, 1, 2, 3, or 4; R⁸ and R^(8a), at each occurrence, areindependently selected from H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄alkynyl and C₃-C₈ cycloalkyl; X is a bond; aryl substituted with 0-3R^(Xb); C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or 5 to 10membered heterocycle substituted with 0-2 R^(Xb); R^(Xb), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ halothioalkoxy; Yis a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—; t is 0, 1, 2, or 3; uis 0, 1, 2, or 3; R⁹ and R^(9a), at each occurrence, are independentlyselected from H, F, C₁-C₆ alkyl and C₃-C₈ cycloalkyl; V is a bond,—C(═O)—, —O—S—, —S(═O), —S(═O)₂—, —N(R¹⁹)—, —C(═O)NR^(19b)—,—NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—,—S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—; Z is H; C₁-C₈ alkyl substitutedwith 1-3 R¹²; C₂-C₄ alkenyl substituted with 1-3 R¹²; C₂-C₄ alkynylsubstituted with 1-3 R¹²; C₁-C₈ alkyl substituted with 0-3 R^(12a);C₂-C₄ alkenyl substituted with 0-3 R^(12a); C₂-C₄ alkynyl substitutedwith 0-3 R^(12a); aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(12b); R¹²,at each occurrence, is independently selected from aryl substituted with0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(12b); R^(12a), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶,—C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R¹⁴ is H, phenyl substituted with 0-4 R^(14b), benzylsubstituted with 0-4 R^(14b), C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆cycloalkyl; R^(14a) is H, C₆-C₁₀ aryl, benzyl, heterocycle, or C₁-C₄alkyl; R^(14b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹⁵, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, aryl-(C₁-C₆ alkyl)- wherein the aryl issubstituted with 0-4 R^(15b), (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—; R^(15b), at each occurrence, is independently selectedfrom H, OH, Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹⁶, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—,and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl,aryl substituted by 0-4 R^(17a), or —CH₂-aryl substituted by 0-4R^(17a); R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃, SO₂CH₃,—NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl; R¹⁸, at each occurrence, isindependently selected from H, C₁-C₆ alkyl, phenyl, benzyl, phenethyl,(C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁹, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, phenyl,benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R²⁰is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, S(═O)₂R¹⁷; C₁-C₆alkyl optionally substituted with 0-2 R^(20a); aryl substituted with 0-4R^(20b); C₃-C₁₀ carbocycle substituted with 0-3 R^(20b); or 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(20b); R^(20a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, F, ═O, CN, NO₂,NR¹⁵R¹⁶, CF₃, aryl substituted with 0-4 R^(20b), and heterocyclesubstituted with 0-4 R^(20b); R^(20b), at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br,I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R²¹, at each occurrence, is independently selected from H,C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionally substitutedwith 0-3 R^(21a); aryl substituted with 0-3 R^(21b); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(21b); and 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(21b); R^(21a), at each occurrence, is independently selected fromH, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃; phenylsubstituted with 0-3 R^(21b); C₃-C₆ cycloalkyl substituted with 0-3R^(21b); and 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(21b); R^(21b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;additionally, two R²¹ substituents on adjacent atoms may be combined toform a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6membered heteroaryl fused radical comprises 1 or 2 heteroatoms selectedfrom N, O, and S; wherein said 5 to 6 membered heteroaryl fused radicalis substituted with 0-3 R²³; additionally, two R²¹ substituents on thesame or adjacent carbon atoms may be combined to form a C₃-C₆ carbocyclesubstituted with 0-3 R²³; additionally, two R²¹ substituents on adjacentatoms may be combined to form a benzo fused radical; wherein said benzofused radical is substituted with 0-4 R²³; R²³, at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br,I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R²⁶ is H; C₁-C₆ alkyl substituted with 0-3R^(26a); C₃-C₁₀ carbocycle substituted with 0-3 R^(26b); or arylsubstituted with 0-3 R^(26b); R^(26a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, aryl and CF₃; and R^(26b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy.
 2. Theprocess according to claim 1 for preparing a compound of Formula I

or a stereoisomer, or a pharmaceutically acceptable salt thereof,wherein: L is —NR²⁶C(═O)—, —C(═O)NR²⁶—, or —OC(═O)NR²⁶—; R³ is—(CHR⁷)_(n)—R⁴, —(CHR⁷)_(l)—N—(CR⁷R^(7a))_(m)—R⁴, or —(CHR⁷)_(l)—O—(CR⁷R^(7a))_(m)—R⁴; n is 0, 1 or 2; m is 0, 1 or 2; l is 1; Ring C is a3 to 8 membered carbocycle substituted with 0-4 R²¹; optionally, thecarbocycle contains a heteroatom selected from —O— and —N(R²⁰)—; R⁴ isH, OH, OR^(14a), C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-2 R^(4a), C₂-C₆ alkynyl substituted with 0-1 R^(4a),C₃-C₆ carbocycle substituted with 0-3 R^(4b), aryl substituted with 0-3R^(4b), or 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(4b); R^(4a), at eachoccurrence, is independently selected from H, OH, F, Cl, Br, I, NR¹⁵R¹⁶,CF₃, C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenyl substitutedwith 0-3 R^(4b), and 5 to 6 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 6 membered heterocycle is substituted with 0-3 R^(4b); R^(4b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R⁶ is H; R⁷, at eachoccurrence, is independently selected from H, OH, F, CF₃, methyl, andethyl; B is

R¹¹ is selected from H, C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂,NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆alkyl optionally substituted with 0-3 R^(11a); aryl substituted with 0-3R^(11b); C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(11b); R^(11a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, CF₃; phenyl substituted with 0-3 R^(11b); C₃-C₆ cycloalkylsubstituted with 0-3 R^(11b); and 5 to 6 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(11b);R^(11b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—; Xis a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆ cycloalkylsubstituted with 0-2 R^(Xb); or 5 to 6 membered heterocycle substitutedwith 0-2 R^(Xb); R^(Xb), at each occurrence, is independently selectedfrom H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; Y is abond, —CH₂—V—, —V—, or —V—CH₂—; V is a bond, —C(═O)—, —O—, —S—, —S(═O)—,—S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—, Z is H; C₁-C₆ alkyl; C₂-C₄alkenyl; C₂-C₄ alkynyl; C₁-C₃ alkyl substituted with 1-2 R¹²; C₂-C₃alkenyl substituted with 1-2 R¹²; C₂-C₃ alkynyl substituted with 1-2R¹²; aryl substituted with 0-4 R^(12b); C₃-C₆ carbocycle substitutedwith 0-3 R^(12b); or 5 to 10 membered heterocycle substituted with 0-3R^(12b); R¹², at each occurrence, is independently selected from arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); R^(12b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹⁴is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl; R^(14a) is H,phenyl, benzyl, or C₁-C₄ alkyl; R¹⁵, at each occurrence, isindependently selected from H, C₁-C₄ alkyl, benzyl, phenethyl, (C₁-C₄alkyl)-C(═O)—, and (C₁-C₄ alkyl)-S(═O)₂—; R¹⁶, at each occurrence, isindependently selected from H, OH, C₁-C₄ alkyl, benzyl, phenethyl,(C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄ alkyl)-S(═O)₂—; R¹⁷ is H, methyl,ethyl, propyl, butyl, methoxymethyl, ethoxymethyl, methoxyethyl,ethoxyethyl, phenyl substituted by 0-3 R^(17a), or —CH₂-phenylsubstituted by 0-3 R^(17a); R^(17a) is H, methyl, methoxy, —OH, F, Cl,CF₃, or OCF₃; R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; R¹⁹, ateach occurrence, is independently selected from H, methyl, and ethyl;R²⁰ is H or C(═O)OR¹⁷; R²⁶ is H, methyl, or ethyl.
 3. The processaccording to claim 2 for preparing a compound of Formula I

or a stereoisomer, or a pharmaceutically acceptable salt thereof,wherein: Ring C is selected from:

wherein Ring C is substituted with 0-2 R²¹; and Ring B is


4. The process according to claim 3 for preparing a compound of FormulaI

or a stereoisomer, or a pharmaceutically acceptable salt thereof,wherein: L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is R⁴, —CH₂OR⁴, or—CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a), C₂-C₆ alkenylsubstituted with 0-1 R^(4a), or C₂-C₆ alkynyl substituted with 0-1R^(4a); R^(4a), at each occurrence, is independently selected from H,OH, F, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3 R^(4b),phenyl substituted with 0-3 R^(4b), and 5 to 6 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 6 membered heterocycle is substituted with0-3 R^(4b); wherein said 5 to 6 membered heterocycle is selected frompyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl,pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl,isoxazolyl, and tetrazolyl; R^(4b), at each occurrence, is independentlyselected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂haloalkyl, and C₁-C₂ haloalkoxy; W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂—or —CH(CH₃)CH₂—; X is a bond, phenyl, C₃-C₆ cycloalkyl, or 5 to 6membered heterocycle; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,—NH—, —N(CH₃)—, or —N(CH₂CH₃)—, Z is H; C₁-C₆ alkyl, C₂-C₄ alkenyl,C₂-C₄ alkynyl, C₁-C₃ alkyl substituted with 1-2 R¹²; C₂-C₃ alkenylsubstituted with 1-2 R¹²; C₂-C₃ alkynyl substituted with 1-2 R¹²; arylsubstituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); or 5 to 6 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(12b); wherein said 5 to6 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxasolyl, andtetrazolyl; R¹², at each occurrence, is independely selected from arylsubstituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulfur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(12b); wherein said 5 to6 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, andtetrazolyl; R^(12b), at each occurrence, is independently selected fromH, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy; R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, orbutyl; R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl; R¹⁶, at each occurrence, isindependently selected from H, OH, methyl, ethyl, propyl, butyl, benzyl,phenethyl, methyl-C(═O)—, ethyl-C(═O)—, methyl-S(═O)₂—, ethyl-S(═O)₂—,and propyl-S(═O)₂—; R¹⁸, at each occurrence, is independently selectedfrom H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;R¹⁹, at each occurrence, is independently selected from H, methyl, andethyl; and R²⁰ is H.
 5. The process according to claim 1 for preparing acompound of Formula (Ia),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —(CR⁷R^(7a))_(n)—R⁴,—(CR⁷R^(7a))_(l)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—O—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴, —(CR⁷R^(7a))_(l)—S(═O)—(CR⁷R^(7a))_(m)—R⁴, —(CR⁷R^(7a))_(l)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—C(═O)N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(l)—N(R^(7b))S(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(l)—S(═O)₂N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴; n is 0, 1, 2, or 3;m is 0, 1, 2, or 3; l is 1, 2, or 3; Ring C is a 3 to 8 memberedcarbocycle, wherein the carbocycle is saturated or partially saturated;optionally, the carbocycle contains a heteroatom selected from —O—, —S—,—S(═O)—, —S(═O)₂—, and —N(R²⁰)—; and wherein the carbocycle issubstituted with 0-4 R²¹; R⁴ is H, OH, OR^(14a), C₁-C₈ alkyl substitutedwith 0-3 R^(4a), C₂-C₈ alkenyl substituted with 0-3 R^(4a), C₂-C₈alkynyl substituted with 0-3 R^(4a), C₃-C₁₀ carbocycle substituted with0-3 R^(4b), aryl substituted with 0-3 R^(4b), or 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₁₀carbocycle substituted with 0-3 R^(4b), aryl substituted with 0-3R^(4b), and 5 to 10 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 10membered heterocycle is substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R⁶ isH; C₁-C₆ alkyl substituted with 0-3 R^(6a); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(6b); or aryl substituted with 0-3 R^(6b);R^(6a), at each occurrence, is independently selected from H, C₁-C₆alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, aryl and CF₃; R^(6b),at each occurrence, is independently selected from H, OH, Cl, F, Br, I,CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, andC₁-C₄ haloalkoxy; R⁷, at each occurrence, is independently selected fromH, OH, Cl, F, Br, I, CN, NO₂, CF₃, C₁-C₄ alkyl, phenyl substituted with0-5 R^(7c); R^(7a), at each occurrence, is independently selected fromH, Cl, F, Br, I, CN, CF₃, and C₁-C₄ alkyl; R^(7b) is independentlyselected from H and C₁-C₄ alkyl; R^(7c), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, CF₃, C₁-C₄ alkoxy,and C₁-C₄ alkyl; B is

R¹¹ is H, C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷,C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionallysubstituted with 0-3 R^(11a); aryl substituted with 0-3 R^(11b); C₃-C₁₀carbocycle substituted with 0-3 R^(11b); and 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(11b); R^(11a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; W is —(CR⁸R^(8a))_(p)—; pis 0, 1, 2, 3, or 4; R⁸ and R^(8a), at each occurrence, areindependently selected from H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄alkynyl and C₃-C₈ cycloalkyl; X is a bond; aryl substituted with 0-3R^(Xb); C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or 5 to 10membered heterocycle substituted with 0-2 R^(Xb); R^(Xb), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ halothioalkoxy; Yis a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—; t is 0, 1, 2, or 3; uis 0, 1, 2, or 3; R⁹ and R^(9a), at each occurrence, are independentlyselected from H, F, C₁-C₆ alkyl and C₃-C₈ cycloalkyl; V is a bond,—C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—, C(═O)NR^(19b)—,—NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—,—S(═O)NR^(19b)—, —C(═O)O—, or —OC(═O)—; Z is H; C₁-C₈ alkyl substitutedwith 1-3 R¹²; C₂-C₄ alkenyl substituted with 1-3 R¹²; C₂-C₄ alkynylsubstituted with 1-3 R¹²; C₁-C₈ alkyl substituted with 0-3 R^(12a);C₂-C₄ alkenyl substituted with 0-3 R^(12a); C₂-C₄ alkynyl substitutedwith 0-3 R^(12a); aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(12b); R¹²,at each occurrence, is independently selected from aryl substituted with0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); and 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(12b); R^(12a), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶,—C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R¹⁴ is H, phenyl substituted with 0-4 R^(14b), benzylsubstituted with 0-4 R^(14b), C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl, or C₃-C₆cycloalkyl; R^(14a) is H, C₆-C₁₀ aryl, benzyl, heterocycle, or C₁-C₄alkyl; R^(14b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹⁵, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, aryl-(C₁-C₆ alkyl)- wherein the aryl issubstituted with 0-4 R^(15b), (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—; R^(15b), at each occurrence, is independently selectedfrom H, OH, Cl, F, Br, I, CN, NO₂, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹⁶, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—,and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁷ is H, C₁-C₆ alkyl, C₂-C₆ alkoxyalkyl,aryl substituted by 0-4 R^(17a), or —CH₂-aryl substituted by 0-4R^(17a); R^(17a) is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, butoxy, —OH, F, Cl, Br, I, CF₃, OCF₃, SCH₃, S(O)CH₃, SO₂CH₃,—NH₂, —N(CH₃)₂, or C₁-C₄ haloalkyl; R¹⁸, at each occurrence, isindependently selected from H, C₁-C₆ alkyl, phenyl, benzyl, phenethyl,(C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R¹⁹, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, phenyl,benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆ alkyl)-S(═O)₂—; R²⁰is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, S(═O)₂R¹⁷; C₁-C₆alkyl optionally substituted with 0-2 R^(20a); aryl substituted with 0-4R^(20b); C₃-C₁₀ carbocycle substituted with 0-3 R^(20b); or 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(20b); R^(20a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, F, ═O, CN, NO₂,NR¹⁵R¹⁶, CF₃, aryl substituted with 0-4 R^(20b), and heterocyclesubstituted with 0-4 R^(20b); R^(20b), at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br,I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R²¹, at each occurrence, is independently selected from H,C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl optionally substitutedwith 0-3 R^(21a); aryl substituted with 0-3 R^(21b); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(21b); and 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(21b); R^(21a), at each occurrence, is independently selected fromH, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃; phenylsubstituted with 0-3 R^(21b); C₃-C₆ cycloalkyl substituted with 0-3R^(21b); and 5 to 6 membered heterocycle containing 1 to 3 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 6membered heterocycle is substituted with 0-3 R^(21b); R^(21b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;additionally, two R²¹ substituents on adjacent atoms may be combined toform a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6membered heteroaryl fused radical comprises 1 or 2 heteroatoms selectedfrom N, O, and S; wherein said 5 to 6 membered heteroaryl fused radicalis substituted with 0-3 R²³; additionally, two R²¹ substituents on thesame or adjacent carbon atoms may be combined to form a C₃-C₆ carbocyclesubstituted with 0-3 R²³; additionally, two R²¹ substituents on adjacentatoms may be combined to form a benzo fused radical; wherein said benzofused radical is substituted with 0-4 R²³; R²³, at each occurrence, isindependently selected from H, OH, C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br,I, CN, NO₂, NR¹⁵R¹⁶, and CF₃; R²⁶ is H; C₁-C₆ alkyl substituted with 0-3R^(26a); C₃-C₁₀ carbocycle substituted with 0-3 R^(26b); or arylsubstituted with 0-3 R^(26b); R^(26a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, aryl and CF₃; and R^(26b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy.
 6. Theprocess according to claim 5 for preparing a compound of Formula (Ia),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴,—CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),C₂-C₆ alkenyl substituted with 0-3 R^(4a), C₂-C₆ alkynyl substitutedwith 0-3 R^(4a), C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenylsubstituted with 0-3 R^(4b), or 5 to 6 membered heterocycle containing 1to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(4b); R^(4a),at each occurrence, is independently selected from is H, OH, F, Cl, Br,I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenylsubstituted with 0-3 R^(4b), or 5 to 6 membered heterocycle containing 1to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(4b); R^(4b),at each occurrence, is independently selected from H, OH, Cl, F, Br, I,CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;Ring C is a 3-6 membered carbocycle selected from:

wherein said 3-6 membered carbocycle is substituted with 0-1 R²¹; R²¹ isselected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy, ethoxy,allyl, and —OCF₃; R¹¹ is H, C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂,NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆alkyl optionally substituted with 0-3 R^(11a); aryl substituted with 0-3R^(11b); C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); and 5 to 10membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(11b); R^(11a), at each occurrence, isindependently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN,NO₂, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; W is a bond, —CH₂—,—CH₂CH₂—; X is a bond; phenyl substituted with 0-1 R^(Xb); C₃-C₆cycloalkyl substituted with 0-1 R^(Xb); or 5 to 6 membered heterocyclesubstituted with 0-1 R^(Xb); R^(Xb) is selected from H, OH, Cl, F,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl,methoxy, ethoxy, propoxy, and —OCF₃; Y is a bond, —C(═O)—, —O—, —S—,—S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkylsubstituted with 0-3 R^(12a); C₂-C₆ alkenyl substituted with 0-3R^(12a); C₂-C₆ alkynyl substituted with 0-3 R^(12a); aryl substitutedwith 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or 5to 10 membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycleis substituted with 0-3 R^(12b); R^(12a), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶,—C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with0-4 R^(12b); or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulfur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(12b); R^(12b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹⁴is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl; R¹⁵, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl,butyl, benzyl, and phenethyl; R¹⁶, at each occurrence, is independentlyselected from H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl,methyl-C(═O)—, ethyl-C(═O)—, methyl-S(═O)₂—, and ethyl-S(═O)₂—; R¹⁸, ateach occurrence, is independently selected from H, methyl, ethyl,propyl, butyl, phenyl, benzyl, and phenethyl; R¹⁹, at each occurrence,is independently selected from H, methyl, ethyl, propyl, and butyl; R²⁰is H or C₁-C₄ alkyl.
 7. The process according to claim 5 for preparing acompound of Formula (Ia),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴,—CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),C₂-C₆ alkenyl substituted with 0-3 R^(4a), or C₂-C₆ alkynyl substitutedwith 0-3 R^(4a); R^(4a), at each occurrence, is independently selectedfrom is H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substitutedwith 0-3 R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b); wherein said 5 to 6 membered heterocycle isselected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, and tetrazolyl; R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; Ring C is selectedfrom:

W is a bond or —CH₂—; X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6membered heterocycle; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,—NH—, —N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkyl substituted with 0-3R^(12a); C₂-C₆ alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynylsubstituted with 0-3 R^(12a); aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); or 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(12b); R^(12a), at each occurrence, is independently selected fromH, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy; phenyl substituted with 0-4 R^(12b); C₃₋₆ carbocyclesubstituted with 0-4 R^(12b); or 5 to 6 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;R¹⁵, at each occurrence, is independently selected from H, methyl,ethyl, propyl, and butyl; and R¹⁶, at each occurrence, is independentlyselected from H, OH, methyl, ethyl, propyl, butyl, benzyl, andphenethyl. R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; R¹⁹, ateach occurrence, is independently selected from H, methyl, ethyl,propyl, and butyl; and R²⁰ is H, methyl, or ethyl.
 8. A processaccording to claim 5 for preparing a compound of Formula (Ia),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; Ring C is selected from:

R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1—NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl—F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—; W is abond or —CH₂—; X is a bond;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or —N(CH₃)—, Zis methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl—F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl, thienyl, pyridyl,2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl,isoxazolyl, 1-benzimidazolyl, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, morpholino, N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl—F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-piperidinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl—F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-piperidinyl)CH₂CH₂—.
 9. The process accordingto claim 5 for preparing a compound of Formula (If),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —(CH₂)_(n)—R⁴,—(CH₂)_(l)—S—R⁴, —(CH₂)_(l)—O—R⁴, or (CH₂)_(l)—N(R^(7b))—R⁴; n is 0, 1or 2; l is 1 or 2; R⁴ is C₁-C₈ alkyl substituted with 0-3 R^(4a), C₂-C₈alkenyl substituted with 0-3 R^(4a), C₂-C₈ alkynyl substituted with 0-3R^(4a), C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), aryl substitutedwith 0-3 R^(4b), or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(4b); R^(4a), ateach occurrence, is independently selected from H, OH, F, Cl, Br, I,NR¹⁵R¹⁶, CF₃, C₃-C₁₀ carbocycle substituted with 0-3 R^(4b), C₆-C₁₀ arylsubstituted with 0-3 R^(4b), and 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(4b);R^(4b), at each occurrence, is independently selected from H, OH, Cl, F,Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄haloalkyl-S—; R^(7b) is H, methyl, or ethyl; Ring C is a 3-8 memberedcarbocycle; wherein said 3-8 membered carbocyclic moiety is saturated orpartially saturated; wherein said 3-8 membered carbocyclic moiety issubstituted with 0-3 R²¹; optionally, the carbocycle contains aheteroatom selected from —O— and —N(R²⁰)—; R²¹, at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, CF₃, acetyl,SCH₃, S(═O)CH₃, S(═O)₂CH₃, NR¹⁵R¹⁶, OR^(14a), C₁-C₄ alkyl, C₂-C₄alkenyl, C₂-C₄ alkynyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹¹ is selected from H, ═O, NR¹⁸R¹⁹, CF₃; C₁-C₄alkyl optionally substituted with 0-1 R^(11a); phenyl substituted with0-3 R^(11b); C₃-C₆ carbocycle substituted with 0-3 R^(11b); and 5 to 7membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycleis substituted with 0-3 R^(11b); wherein said 5 to 7 memberedheterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl,thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl,imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;R^(11a), at each occurrence, is independently selected from H, C₁-C₄alkyl, OR¹⁴, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3R^(11b); R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is a bond, —CH₂—,—CH₂CH₂—; X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆cycloalkyl substituted with 0-2 R^(Xb); or 5 to 6 membered heterocyclesubstituted with 0-2 R^(Xb); R^(Xb), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,—N(R¹⁹)—, —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,—S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or—OC(═O)—; Z is H; C₁-C₈ alkyl substituted with 0-3 R^(12a); C₂-C₆alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynyl substituted with 0-3R^(12a); aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); or 5 to 10 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 10 membered heterocycle is substituted with 0-3 R^(12b);R^(12a), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, —C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,C₁-C₄ haloalkyl-S—, aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocyclesubstituted with 0-4 R^(12b); and 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(12b); R^(12b), at each occurrence, is independently selected fromH, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy,and C₁-C₄ haloalkyl-S—; R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, C₂-C₆alkoxyalkyl, or C₃-C₆ cycloalkyl; R^(14a) is H, phenyl, benzyl, or C₁-C₄alkyl; R¹⁵, at each occurrence, is independently selected from H, C₁-C₆alkyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and (C₁-C₆alkyl)-S(═O)₂—; R¹⁶, at each occurrence, is independently selected fromH, OH, C₁-C₆ alkyl, benzyl, phenethyl, (C₁-C₄ alkyl)-C(═O)—, and (C₁-C₄alkyl)-S(═O)₂—; R¹⁸, at each occurrence, is independently selected fromH, C₁-C₆ alkyl, phenyl, benzyl, phenethyl, (C₁-C₆ alkyl)-C(═O)—, and(C₁-C₆ alkyl)-S(═O)₂—; R¹⁹, at each occurrence, is independentlyselected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, andphenethyl; and R²⁰ is H or C₁-C₄ alkyl.
 10. The process according toclaim 5 for preparing a compound of Formula (If),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴,—CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),C₂-C₆ alkenyl substituted with 0-3 R^(4a), C₂-C₆ alkynyl substitutedwith 0-3 R^(4a), C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenylsubstituted with 0-3 R^(4b), or 5 to 6 membered heterocycle containing 1to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(4b); R^(4a),at each occurrence, is independently selected from is H, OH, F, Cl, Br,I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substituted with 0-3 R^(4b), phenylsubstituted with 0-3 R^(4b), or 5 to 6 membered heterocycle containing 1to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(4b); R^(4b),at each occurrence, is independently selected from H, OH, Cl, F, Br, I,CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—;Ring C is a 3-6 membered carbocycle; wherein said 3-6 memberedcarbocyclic moiety is saturated or partially unsaturated; wherein said3-6 membered carbocyclic moiety is substituted with 0-2 R²¹; optionally,the carbocycle contains a heteroatom selected from —O— and —N(R²⁰)—;R²¹, at each occurrence, is independently selected from H, OH, Cl, F,Br, I, CN, NO₂, CF₃, acetyl, SCH₃, methyl, ethyl, methoxy, ethoxy,allyl, —OCF₃, and —SCF₃; R¹¹ is selected from H, ═O, NR¹⁸R¹⁹, CF₃; C₁-C₄alkyl optionally substituted with 0-1 R^(11a); phenyl substituted with0-3 R^(11b); C₃-C₆ carbocycle substituted with 0-3 R^(11b); and 5 to 7membered heterocycle containing 1 to 4 heteroatoms selected fromnitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycleis substituted with 0-3 R^(11b); wherein said 5 to 7 memberedheterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl,thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl,imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;R^(11a), at each occurrence, is independently selected from H, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ═O,NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl,and C₁-C₂ haloalkoxy; W is a bond, —CH₂—, —CH₂CH₂—; X is a bond; phenylsubstituted with 0-1 R^(Xb); C₃-C₆ cycloalkyl substituted with 0-1R^(Xb); or 5 to 6 membered heterocycle substituted with 0-1 R^(Xb);R^(Xb) is selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, methoxy, ethoxy, propoxy,and —OCF₃; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkyl substituted with 0-3R^(12a); C₂-C₆ alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynylsubstituted with 0-3 R^(12a); C₆-C₁₀ aryl substituted with 0-4 R^(12b);C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or 5 to 10 memberedheterocycle containing 1 to 4 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 10 membered heterocycle issubstituted with 0-3 R^(12b); R^(12a), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶,—C(═O)NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl,C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkyl-S—,C₆-C₁₀ aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substitutedwith 0-4 R^(12b); or 5 to 10 membered heterocycle containing 1 to 4heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5to 10 membered heterocycle is substituted with 0-3 R^(12b); R^(12b), ateach occurrence, is independently selected from H, OH, Cl, F, Br, I, CN,NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; R¹⁴is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl; R¹⁵, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl,butyl, benzyl, and phenethyl; R¹⁶, at each occurrence, is independentlyselected from H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl,methyl-C(═O)—, ethyl-C(═O)—, methyl-S(═O)₂—, and ethyl-S(═O)₂—; R¹⁸, ateach occurrence, is independently selected from H, methyl, ethyl,propyl, butyl, phenyl, benzyl, and phenethyl; R¹⁹, at each occurrence,is independently selected from H, methyl, ethyl, propyl, and butyl; R²⁰is H or C₁-C₄ alkyl.
 11. The process according to claim 10 for preparinga compound of Formula (If),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; R³ is —R⁴, —CH₂R⁴, —CH₂CH₂R⁴,—CH₂OR⁴, or —CH₂CH₂OR⁴; R⁴ is C₁-C₆ alkyl substituted with 0-3 R^(4a),C₂-C₆ alkenyl substituted with 0-3 R^(4a), or C₂-C₆ alkynyl substitutedwith 0-3 R^(4a); R^(4a), at each occurrence, is independently selectedfrom is H, OH, F, Cl, Br, I, NR¹⁵R¹⁶, CF₃, C₃-C₆ carbocycle substitutedwith 0-3 R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to 6 memberedheterocycle containing 1 to 3 heteroatoms selected from nitrogen,oxygen, and sulphur, wherein said 5 to 6 membered heterocycle issubstituted with 0-3 R^(4b); wherein said 5 to 6 membered heterocycle isselected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, and tetrazolyl; R^(4b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ haloalkyl-S—; Ring C is a 3-6membered carbocycle selected from:

wherein said 3-6 membered carbocycle is substituted with 0-1 R²¹; R²¹ isselected from H, OH, Cl, F, CN, CF₃, methyl, ethyl, methoxy, ethoxy,allyl, and —OCF₃; R¹¹ is selected from H, ═O, NR¹⁸R¹⁹; C₁-C₄ alkyloptionally substituted with 0-1 R^(11a); phenyl substituted with 0-3R^(11b); 5 to 7 membered heterocycle containing 1 to 4 heteroatomsselected from nitrogen, oxygen, and sulphur, wherein said 5 to 7membered heterocycle is substituted with 0-3 R^(11b); wherein said 5 to7 membered heterocycle is selected from pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl,piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,homopiperidinyl, and tetrazolyl; R^(11a), at each occurrence, isindependently selected from H, methyl, ethyl, propyl, methoxy, ethoxy,propoxy, phenoxy, F, Cl, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with0-3 R^(11b); R^(11b), at each occurrence, is independently selected fromH, OH, Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy,ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is a bond or—CH₂—; X is a bond, phenyl, C₃-C₆ cycloalkyl or 5 to 6 memberedheterocycle; Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—,—N(CH₃)—, or —N(CH₂CH₃)—; Z is H; C₁-C₈ alkyl substituted with 0-3R^(12a); C₂-C₆ alkenyl substituted with 0-3 R^(12a); C₂-C₆ alkynylsubstituted with 0-3 R^(12a); aryl substituted with 0-4 R^(12b); C₃-C₁₀carbocycle substituted with 0-4 R^(12b); or 5 to 10 membered heterocyclecontaining 1 to 4 heteroatoms selected from nitrogen, oxygen, andsulphur, wherein said 5 to 10 membered heterocycle is substituted with0-3 R^(12b); R^(12a), at each occurrence, is independently selected fromH, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy; phenyl substituted with 0-4 R^(12b); C₃₋₆ carbocyclesubstituted with 0-4 R^(12b); or 5 to 6 membered heterocycle containing1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, whereinsaid 5 to 6 membered heterocycle is substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;R¹⁵, at each occurrence, is independently selected from H, methyl,ethyl, propyl, and butyl; and R¹⁶, at each occurrence, is independentlyselected from H, OH, methyl, ethyl, propyl, butyl, benzyl, andphenethyl. R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; R¹⁹, ateach occurrence, is independently selected from H, methyl, ethyl,propyl, and butyl; and R²⁰ is H, methyl, or ethyl.
 12. The processaccording to claim 11 for preparing a compound of Formula (If),

a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:L is —NHC(═O)—, —C(═O)NH—, or —OC(═O)NH—; Ring C is selected from:

R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH(OH)CH₂CH(CH₃)₂, —CH(OH)CH(CH₃)₂,—CH(NH₂)CH₂CH(CH₃)₂, —CH₂CH₂OCH₃, —CH₂OCH₂CH₃, —CF₂CH₂CH(CH₃)₂,—CH(NHCH₃)CH₂CH(CH₃)₂, —CH(NHSO₂CH₂CH₂CH₃)CH₂CH(CH₃)₂, cyclohexyl-,cyclopentyl-, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,cyclopentyl-CH₂CH₂—, cyclohexyl-CH(OH)—, cyclohexyl-CH₂CH₂—,1—NH₂-cyclopentyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl—F-phenyl)CH₂—, phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—,(3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,(3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,(2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,(2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,(3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,(2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,(2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,(3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,(3-F-5-Cl-phenyl)CH₂CH₂—, 4-piperidinyl-CH₂CH₂—, phenyl-CH₂CH₂CF₂—,phenyl-CH₂CH(OH)—, imidazolyl-CH₂CH(OH)—, or phenyl-CH₂OCH₂—; W is abond or —CH₂—; X is a bond;

Y is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or —N(CH₃)—, Zis methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl,t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl,2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl,3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl,2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl,3-F-5-Cl-phenyl, 3-Cl—F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl,4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl,3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl,furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl,1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, morpholino, N-piperinyl,phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—,(2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂, (4-Cl-phenyl)CH₂—,(2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—,(2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—,(2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—,(2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—,(3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—, (3-Cl—F-phenyl)CH₂—,(2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—,(2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—,(2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—,(2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—,(furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—, (2-Me-pyridyl)CH₂—,(3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—, (1-imidazolyl)CH₂—,(oxazolyl)CH₂—, (isoxazolyl)CH₂—, (1-benzimidazolyl)CH₂—,(cyclopropyl)CH₂—, (cyclobutyl)CH₂—, (cyclopentyl)CH₂—,(cyclohexyl)CH₂—, (morpholino)CH₂—, (N-piperidinyl)CH₂—, phenyl-CH₂CH₂—,(phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—,(4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—,(4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl—F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, or (N-piperidinyl)CH₂CH₂—; and R¹¹, at eachoccurrence, is independently selected from H, ═O, methyl, ethyl, phenyl,benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—,3-F-phenyl, (3-F-phenyl)CH₂—, (3-F-phenyl)CH₂CH₂—, 2-F-phenyl,(2-F-phenyl)CH₂—, (2-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂CH₂—, 3-Cl-phenyl, (3-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 3-CH₃-phenyl, (3-CH₃-phenyl)CH₂—,(3-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—,(4-CF₃-phenyl)CH₂CH₂—, cyclopentyl, pyrid-2-yl, pyrid-3-yl, andpyrid-4-yl.
 13. A process according to claim 5 for preparing amalonamide compound, or a stereoisomer or pharmaceutically acceptablesalt thereof, wherein the product is (2S)—N-{[N-(1-{[3-(4Fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopropyl}-2-hydroxy-4-methylpentanamide

¹H NMR (300 MHz, CD₃OD) δ 7.00-6.70 (m, 8H), 4.45 (m, 5H), 4.15 (m, 1H),3.10-3.40 (m, 2H), 2.00-1.00 (m, 12H), 0.90, (m, 6H). MS [M+H]⁺
 526. 14.A process according to claim 5 for preparing a malonamide compound, or astereoisomer or pharmaceutically acceptable salt thereof, wherein theproduct is(2S)-N-{[N-(1-{[3-(4-Fluorophenoxy)phenyl]methyl}-2-oxoazaperhydroepin-3-yl)carbamoyl]cyclopentyl}-2-hydroxy-3-methylbutanamide

¹H NMR (300 MHz, CD₃OD) δ 7.20-6.80 (m, 8H), 4.60 (m, 3H), 4.00 (d, 1H),3.5 (m, 1H), 3.20 (m, 1H), 2.40-1.05 (m, 17H), 1.00 (d, 3H), 0.90 (d,3H). MS [M+H]⁺
 540. 15. A process of preparing a pharmaceuticalcomposition comprising combining a compound prepared by the processaccording to claim 1, and a pharmaceutically acceptable carrier.
 16. Aprocess of preparing a pharmaceutical composition comprising combining acompound prepared by the process according to claim 2, and apharmaceutically acceptable carrier.
 17. A process of preparing apharmaceutical composition comprising combining a compound prepared bythe process according to claim 3, and a pharmaceutically acceptablecarrier.
 18. A process of preparing a pharmaceutical compositioncomprising combining a compound prepared by the process according toclaim 4, and a pharmaceutically acceptable carrier.
 19. A process ofpreparing a pharmaceutical composition comprising combining a compoundprepared by the process according to claim 5, and a pharmaceuticallyacceptable carrier.
 20. A process of preparing a pharmaceuticalcomposition comprising combining a compound prepared by the processaccording to claim 6, and a pharmaceutically acceptable carrier.
 21. Aprocess of preparing a pharmaceutical composition comprising combining acompound prepared by the process according to claim 7, and apharmaceutically acceptable carrier.
 22. A process of preparing apharmaceutical composition comprising combining a compound prepared bythe process according to claim 8, and a pharmaceutically acceptablecarrier.
 23. A process of preparing a pharmaceutical compositioncomprising combining a compound prepared by the process according toclaim 9, and a pharmaceutically acceptable carrier.
 24. A process ofpreparing a pharmaceutical composition comprising combining a compoundprepared by the process according to claim 10, and a pharmaceuticallyacceptable carrier.
 25. A process of preparing a pharmaceuticalcomposition comprising combining a compound prepared by the processaccording to claim 11, and a pharmaceutically acceptable carrier.
 26. Aprocess of preparing a pharmaceutical composition comprising combining acompound prepared by the process according to claim 12, and apharmaceutically acceptable carrier.
 27. A process of preparing apharmaceutical composition comprising combining a compound prepared bythe process according to claim 13, and a pharmaceutically acceptablecarrier.
 28. A process of preparing a pharmaceutical compositioncomprising combining a compound prepared by the process according toclaim 14, and a pharmaceutically acceptable carrier.